Scientific Bibliography

Nanobiology and Cancer Nanotechnology
Nanotechnology Devices and Nanomaterials
Nanotechnology-Enabled Therapeutics Development and Delivery
Cancer Diagnostics and Biosensors
Nanotechnologies in Advanced Imaging
Environment, Health and Safety

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Nanotechnology Devices and Nanomaterials

2007  2006   2005   2004   2003   2002

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Light-assisted oxidation of single-wall carbon nanohorns for abundant creation of oxygenated groups that enable chemical modifications with proteins to enhance biocompatibility.
Minfang Zhang, Masako Yudasaka, Kumiko Ajima, Jin Miyawaki, Sumio Iijima.
ACS Nano. 2007;1(4), 265–272.
[ expand abstract ]

We show that light-assisted oxidation with hydrogen peroxide effectively and rapidly opens holes in carbon nanohorn walls and, more importantly, creates abundant oxygenated groups such as carboxylic groups at the hole edges. These oxygenated groups reacted with the protein bovine serum albumin. The obtained conjugates were highly dispersed in phosphate-buffered saline and were taken up by cultured mammalian cells via an endocytosis pathway.

Amphiphilic helical peptide enhances the uptake of single-walled carbon nanotubes by living cells.
Chin SF, Baughman RH, Dalton AB, Dieckmann GR, Draper RK, Mikoryak C, Musselman IH, Poenitzsch VZ, Xie H, Pantano P.
Exp Biol Med (Maywood). 2007 Oct;232(9):1236-44.
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Department of Chemistry, The University of Texas at Dallas, Richardson, TX 75083-0688, USA. The success of many projected applications of carbon nano-tubes (CNTs) to living cells, such as intracellular sensors and nanovectors, will depend on how many CNTs are taken up by cells. Here we report the enhanced uptake by HeLa cells of single-walled CNTs coated with a designed peptide termed nano-1. Atomic force microscopy showed that the dispersions were composed of individual and small bundles of nano-1 CNTs with 0.7- to 32-nm diameters and 100- to 400-nm lengths. Spectroscopic characterizations revealed that nano-1 disperses CNTs in a non-covalent fashion that preserves CNT optical properties. Elemental analyses indicated that our sample preparation protocol involving sonication and centrifugation effectively eliminated metal impurities associated with CNT manufacturing processes. We further showed that the purified CNT dispersions are taken up by HeLa cells in a time- and temperature-dependent fashion, and that they do not affect the HeLa cell growth rate, evidence that the CNTs inside cells are not toxic under these conditions. Finally, we discovered that approximately 6-fold more CNTs are taken up by cells in the presence of nano-1 compared with medium containing serum but no peptide. The fact that coating CNTs with a peptide enhances uptake offers a strategy for improving the performance of applications that require CNTs to be inside cells.

Dendrimer generation effects on photodynamic efficacy of dendrimer porphyrins and dendrimer-loaded supramolecular nanocarriers.
Li Y, Jang WD, Nishiyama N, Kishimura A, Kawauchi S, Morimoto Y, Miake S, Yamashita T, Kikuchi M, Aida T, Kataoka K.
Chem. Mater. 2007; 19 (23), 5557 -5562.
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A series of poly(benzyl ether) dendrimer porphyrins (DPs) (Gn = n-generation dendrimer, n = 1-3) was examined as potential photosensitizers for photodynamic therapy (PDT). Polyion complexes (PICs) between the DPs and poly(ethylene glycol)-block-poly(L-lysine) (PEG-b-PLL) were formed via an electrostatic interaction between the positively charged poly(L-lysine) (PLL) segment and negatively charged periphery of the DPs. Dynamic light scattering (DLS) measurements and transmission electron microscopy (TEM) showed that G3 formed a core-shell-type nanocarrier micelle, whereas G1 and G2 formed irregular-shaped nanoparticles with a relatively high polydispersity. The photophysical properties of the DP-loaded PIC nanocarriers strongly depend on the generation of the DPs. In the case of G1 and G2, their fluorescence lifetime and oxygen consumption ability were significantly reduced by the formation of the PIC nanocarriers, whereas the G3-loaded PIC nanocarrier exhibited almost comparable fluorescence lifetimes and oxygen consumption abilities to the free G3. The incorporation of DPs into PIC nanocarriers resulted in an appreciable increase in the cellular uptake, yet inversely correlated with the generation. Alternatively, the photocytotoxicity of the DPs within the nanocarriers increased with an increase in the generation despite a decrease in the cellular uptake. By correlating the effects of the uptake amount with the photocytotoxicity, the PIC nanocarriers showed remarkable enhancement of the PDT efficacy dependent on the generation of DPs.

Biocatalytic microcontact printing.
Snyder PW, Johannes MS, Vogen BN, Clark RL, Toone EJ.
J Org Chem. 2007 Sep 14;72(19):7459-61.
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Immobilized biocatalytic lithography is presented as an application of soft lithography. In traditional microcontact printing, diffusion limits resolution of pattern transfer. By using an immobilized catalyst, the lateral resolution of microcontact printing would depend only on the length and flexibility of the tether (<2 nm) as opposed to diffusion (>100 nm). In the work, exonuclease reversibly immobilized on a relief-patterned stamp is used to ablate ssDNA monolayers Percent of ablation was determined via confocal fluorescence microscopy to be approximately 70%.

Glutaric acid as a spacer facilitates improved intracellular uptake of LHRH-SPION into human breast cancer cells.
Kumar CS, Leuschner C, Urbina M, Ozkaya T, Hormes J.
Int J Nanomedicine. 2007;2(2):175-9.
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Superparamagnetic iron oxide nanoparticles (SPIONs) bound directly to luteinizing hormone releasing hormone (LHRH) have shown high efficiency for intracellular uptake to breast cancer cells, MDA-MB-435S.luc. We demonstrate in this communication that inclusion of a small spacer molecule such as glutaric acid (Glu) in between SPION and LHRH increases further receptor mediated intracellular uptake. LHRH-bound SPIONs with and without the spacer molecule were nontoxic.

Selecting clinically-driven biomarkers for cancer nanotechnology.
Phan JH, Young AN, Wang MD.
Conf Proc IEEE Eng Med Biol Soc. 2006;1:3317-20.
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The challenge of biomarker identification for bionanotechnology is that we need to find less than ten potential biomarkers from high throughput data so that quantum dot synthesis and imaging can be effective. Among all the extensive biomarker research, the novelty of our research is to reduce the number the biomarkers by studying the efficacy of several classifiers and error estimation methods. Specifically, we are using renal cancer expression data. The dataset consists of 31 microarray samples divided into four classes-clear cell, oncocytoma/chromophobe, papillary, and angiomyolipoma. Each class is compared to all other classes using error estimation methods for support vector machines (SVM), Fisher's discriminant (FD), and signed distance function (SDF). Prior knowledge of significant biomarker from a previous study is used to score the effectiveness of each classifier in correctly identifying these biomarkers. We have achieved intelligent model selection for biomarker identification so that the total number of nano-imaging targets is small.

Nanotechnology and Cancer.
Heath JR, Davis ME.
Annu Rev Med. 2008;59:251-65.
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The biological picture of cancer is rapidly advancing from models built from phenomenological descriptions to network models derived from systems biology, which can capture the evolving pathophysiology of the disease at the molecular level. The translation of this (still academic) picture into a clinically relevant framework can be enabling for the war on cancer, but it is a scientific and technological challenge. In this review, we discuss emerging in vitro diagnostic technologies and therapeutic approaches that are being developed to handle this challenge. Our discussion of in vitro diagnostics is guided by the theme of making large numbers of measurements accurately, sensitively, and at very low cost. We discuss diagnostic approaches based on microfluidics and nanotechnology. We then review the current state of the art of nanoparticle-based therapeutics that have reached the clinic. The goal of the presentation is to identify nanotherapeutic strategies that are designed to increase efficacy while simultaneously minimizing the toxic side effects commonly associated with cancer chemotherapies.

Supramolecular Chemistry on Water-Soluble Carbon Nanotubes for Drug Loading and Delivery.
Liu Z, Sun X, Nakayama-Ratchford N, Dai H.
ACS Nano. 2007;1(1):50–56.
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We show that large surface areas exist for supramolecular chemistry on single-walled carbon nanotubes (SWNTs) prefunctionalized noncovalently or covalently by common surfactant or acid-oxidation routes. Water-soluble SWNTs with poly(ethylene glycol) (PEG) functionalization via these routes allow for surprisingly high degrees of p-stacking of aromatic molecules, including a cancer drug (doxorubicin) with ultrahigh loading capacity, a widely used fluorescence molecule (fluorescein), and combinations of molecules. Binding of molecules to nanotubes and their release can be controlled by varying the pH. The strength of p-stacking of aromatic molecules is dependent on nanotube diameter, leading to a method for controlling the release rate of molecules from SWNTs by using nanotube materials with suitable diameter. This work introduces the concept of “functionalization partitioning” of SWNTs, i.e., imparting multiple chemical species, such as PEG, drugs, and fluorescent tags, with different functionalities onto the surface of the same nanotube. Such chemical partitioning should open up new opportunities in chemical, biological, and medical applications of novel nanomaterials.

Surface modification and functionalization of nanoscale metal-organic frameworks for controlled release and luminescence sensing.
Rieter WJ, Taylor KM, Lin W.
J Am Chem Soc. 2007 Aug 15;129(32):9852-3.
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We describe in this paper a general method for synthesizing a new class of nanocomposites with a nanoscale metal-organic framework (NMOF) core and a silica shell. Silica shells of variable thickness were deposited on the NMOFs that had been surface-modified with polyvinylpyrrolidone (PVP) using a sol-gel procedure. The NMOF core of the nanocomposite could be completely removed (via dissolution) at low pH to afford hollow silica shells with varied thickness and aspect ratios. We also showed that the silica shell of such nanocomposites significantly stabilized the NMOF core against dissolution, thus demonstrating the ability to control the release of metal constituents from such silica-coated NMOFs. The silica shell was further functionalized with a silylated Tb-EDTA monoamide derivative for the luminescence sensing of dipicolinic acid (DPA), which is a major constituent of many pathogenic spore-forming bacteria. Owing to the tunability of NMOF composition and morphology, the present approach should allow for the synthesis of not only interesting nanoshells that are not accessible with presently available templates but also novel core-shell hybrid nanostructures for future imaging, sensing, and drug delivery applications.

Hydrodynamic dimensions, electrophoretic mobility, and stability of hydrophilic quantum dots.
Pons T, Uyeda HT, Medintz IL, Mattoussi H.
J Phys Chem B. 2006 Oct 19;110(41):20308-16.
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Luminescent semiconductor quantum dots (QDs) have great potential for use in biological assays and imaging. These nanocrystals are capped with surface ligands (bifunctional molecules, amphiphilic polymers, phospholipids, etc.) that render them hydrophilic and provide them with functional properties. These coatings alters their hydrodynamic radii and surface charge, which can drastically affect properties such as diffusion within the cell cytoplasm. Heavy atom techniques such as transmission electron microscopy and X-ray scattering probe the inorganic core and do not take into account the ligand coating. Herein we use dynamic light scattering to characterize the hydrodynamic radius (R(H)) of CdSe-ZnS QDs capped with various hydrophilic surface coatings (including dihydrolipoic acid and amphiphilic polymers) and self-assembled QD-protein bioconjugates. Experiments were complemented with measurements of the geometric size and zeta potential using agarose gel electrophoresis and laser Doppler velocimetry. We find that the effects of surface ligands on the hydrodynamic radius and on the nanoparticle mobility are complex and strongly depend on a combination of the inorganic core size and nature and lateral extension of the hydrophilic surface coating. These properties are critical for the design of QD-based biosensing assays as well as QD bioconjugate diffusion in live cells.

Influence of size, surface, cell line, and kinetic properties on the specific binding of A33 antigen-targeted multilayered particles and capsules to colorectal cancer cells.
Christina Cortez, Eva Tomaskovic-Crook, Angus P. R. Johnston, Andrew M. Scott, Edouard C. Nice, Joan K. Heath, Frank Caruso.
ACS Nano. 2007;1(2):93–102.
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There has been increased interest in the use of polymer capsules formed by the layer-by-layer (LbL) technique as therapeutic carriers to cancer cells due to their versatility and ease of surface modification. We have investigated the influence of size, surface properties, cell line, and kinetic parameters such as dosage (particle concentration) and incubation time on the specific binding of humanized A33 monoclonal antibody (huA33 mAb)-coated LbL particles and capsules to colorectal cancer cells. HuA33 mAb binds to the A33 antigen present on almost all colorectal cancer cells and has demonstrated great promise in clinical trials as an immunotherapeutic agent for cancer therapy. Flow cytometry experiments showed the cell binding specificity of huA33 mAb-coated particles to be size-dependent, with the optimal size for enhanced selectivity at ~500 nm. The specific binding was improved by increasing the dosage of particles incubated with the cells. The level of specific versus nonspecific binding was compared for particles terminated with various polyelectrolytes to examine the surface dependency of antibody attachment and subsequent cell binding ability. The specific binding of huA33 mAb-coated particles is also reported for two colorectal cancer cell lines, with an enhanced binding ratio between 4 and 10 obtained for the huA33 mAb-functionalized particles. This investigation aims to improve the level of specific targeting of LbL particles, which is important in targeted drug and gene delivery applications.

Dendrimer-mediated transfer printing of DNA and RNA microarrays.
Rozkiewicz DI, Brugman W, Kerkhoven RM, Ravoo BJ, Reinhoudt DN.
J Am Chem Soc. 2007 Sep 19;129(37):11593-9.
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This paper describes a new method to replicate DNA and RNA microarrays. The technique, which facilitates positioning of DNA and RNA with submicron edge resolution by microcontact printing (muCP), is based on the modification of poly(dimethylsiloxane) (PDMS) stamps with dendrimers ("dendri-stamps"). The modification of PDMS stamps with generation 5 poly(propylene imine) dendrimers (G5-PPI) gives a high density of positive charge on the stamp surface that can attract negatively charged oligonucleotides in a "layer-by-layer" arrangement. DNA as well as RNA is transfer printed from the stamp to a target surface. Imine chemistry is applied to immobilize amino-modified DNA and RNA molecules to an aldehyde-terminated substrate. The labile imine bond is reduced to a stable secondary amine bond, forming a robust connection between the polynucleotide strand and the solid support. Microcontact printed oligonucleotides are distributed homogeneously within the patterned area and available for hybridization. By using a robotic spotting system, an array of hundreds of oligonucleotide spots is deposited on the surface of a flat, dendrimer-modified stamp that is subsequently used for repeated replication of the entire microarray by microcontact printing. The printed microarrays are characterized by homogeneous probe density and regular spot morphology.

Fluorescent magnetic nanocrystals by sequential addition of reagents in a one-pot reaction: a simple preparation for multifunctional nanostructures.
Gao J, Zhang B, Gao Y, Pan Y, Zhang X, Xu B.
J Am Chem Soc. 2007 Oct 3;129(39):11928-35.
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Core-shell nanostructures consisting of FePt magnetic nanoparticles as the core and semiconducting chalcogenides as the shell were synthesized by a series of reactions in a one-pot procedure. Adding Cd(acac)2 as the cadmium precursor to a reaction mixture containing FePt nanoparticles afforded FePt@CdO core-shell intermediates. The subsequent addition of chalcogens yielded FePt@CdX core-shell nanocrystals (where X was S or Se). The reverse sequence of addition, i.e., adding X before Cd, resulted in spongelike nanostructures because the chalcogens readily formed nanowires in the solution. Transmission electron microscopy, energy-dispersive X-ray spectrometry, selected area electron diffraction, fluorescence spectroscopy, and SQUID were used to characterize the nanostructures. These core-shell nanostructures displayed superparamagnetism at room temperature and exhibited fluorescence with quantum yields of 2.3-9.7%. The flexibility in the sequence of addition of reagents, combined with the compatibility of the lattices of the different materials, provides a powerful yet convenient strategy for generating sophisticated, multifunctional nanostructures.

Facile production of multivalent enzyme-nanoparticle conjugates.
Kuhna SJ, Fincha SK, Hallahana DE, Giorgioa TD.
J Magn Magn Mater. 2007 April;311(1):68-72
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Nanoparticles (NPs) enable the development of new, biologically relevant, multifunctional agents. Multifunctional NPs can mimic the invasive biological processes involved in cancer metastasis. We have demonstrated a facile and controllable method of conjugating multiple enzyme species to superparamagnetic (SPM) NPs. Horseradish peroxidase, a-glucosidase, and collagenase were conjugated to SPM NPs with a functional enzyme:NP ratio of 15:127:103:1. N-succinimidyl-S-acetylthiopropionate (SATP)-mediated addition of sulfhydryls to enzymes was achieved without significant activity loss. Conjugation of all enzymes was simultaneously accomplished using maleimide reactive groups generated from activation of amines associated with polyethylene glycol molecules on the NP surface. Cross reactivity between enzyme activity assay systems was negligible.

Integrated magnetic bionanocomposites through nanoparticle-mediated assembly of ferritin.
Srivastava S, Samanta B, Jordan BJ, Hong R, Xiao Q, Tuominen MT, Rotello VM.
J Am Chem Soc. 2007 Sep 26;129(38):11776-80.
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Magnetic (FePt) and nonmagnetic (Au) nanoparticles were used to assemble ferritin into near-monodisperse bionanocomposites featuring regular interparticle spacing. The FePt/ferritin assemblies are integrated magnetic materials with ferritin providing added magnetic volume fraction to the magnetic nanocomposite. These assemblies differ from either of their constituent particles in terms of blocking temperature (TB), net magnetic moment, coercivity, and remnance.

Surface modification of cetyltrimethylammonium bromide-capped gold nanorods to make molecular probes.
Yu C, Varghese L, Irudayaraj J.
Langmuir. 2007 Aug 14; 23(17):9114-9.
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A chemical procedure to replace the cetyltrimethylammonium bromide (CTAB) cap on gold nanorods (GNRs) fabricated through seed-mediated growth with organothiol compounds [3-animo-5-mercapto-1,2,4-triazole (AMTAZ) and 11-mercaptoundecaonic acid (MUDA)] was developed to reduce the cytotoxity of GNRs and facilitate further biofunctionalization. Compared to phosphatidylcholine (PC) modification, our procedure yields stable GNRs that are biocompatible and suitable for whole-cell studies. The PC-, AMTAZ-, and MUDA-activated GNRs all showed low cytotoxicity. By choosing different organothiols, net positive or negative charges could be created on the nanorod surface, for different applications. Gold nanorod molecular probes (GNrMPs) were fabricated by subsequent attachment of antibodies to the activated GNRs and were used to visualize and detect cell surface biomarkers in normal and transformed human breast epithelial cells, demonstrating the potential of developing novel biosensors using gold nanorods. The sensitivity of GNrMPs made from organothiol-activated GNRs is considerably higher than that of CTAB/PC-activated GNRs, demonstrating that the protocol reported here is favored in developing molecular probes using GNRs.

The efficiency of a PAMAM dendrimer toward the encapsulation of the antileukemic drug 6-mercaptopurine.
Neerman MF.
Anticancer Drugs. 2007 Aug;18(7):839-42.
[ expand abstract ]

No abstract available (Citation link)

Locked nucleic acid-nanoparticle conjugates.
Seferos DS, Giljohann DA, Rosi NL, Mirkin CA.
Chembiochem. 2007 Jul 23;8(11):1230-2.
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No abstract available (Citation link)

Simplified preparation via streptavidin of antisense oligomers/carriers nanoparticles showing improved cellular delivery in culture.
Wang Y, Nakamura K, Liu X, Kitamura N, Kubo A, Hnatowich DJ.
Bioconjug Chem. 2007 Jul-Aug;18(4):1338-43.
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OBJECTIVE: Carriers are increasingly now viewed as helpful or even essential to improve cellular uptake in connection with antisense tumor targeting and other applications requiring transmembrane delivery of oligomers. Evaluation of many of the large number of available and potentially useful carriers is limited only by the complexities of preparing the oligomer/carriers by covalent conjugation. However, using streptavidin as a linker between biotinylated carriers and biotinylated antisense oligomers would require only simple mixing for preparation. The goal of this study was to evaluate the preparation and cell accumulation in culture of carrier/streptavidin nanoparticle of an antisense phosphorodiamide morpholino (MORF) oligomer. METHODS: The model carriers were cholesterol, a 10 mer HIV-tat peptide, and a 10 mer polyarginine, each having been reported elsewhere to improve cellular delivery of oligomers. The model antisense oligomer was the 25 mer MORF targeting the survivin mRNA. The accumulations of the antisense MORF/carrier nanoparticle were compared to the sense MORF/carrier, to the carrier-free nanoparticles, and to the naked antisense MORF in the survivin-expressing MCF-7 cells. The MORFs and peptides were purchased biotinylated, while the cholesterol was biotinylated in-house. In all cases, the 99mTc radiolabel was placed on the oligomers. Cell studies were performed at low nM concentration as required for antisense imaging applications and at 37 degrees C primarily in 1% FBS. RESULTS: Each radiolabeled oligomer/streptavidin/carrier nanoparticle was successfully prepared by careful mixing at a 1:1 molar ratio. As evidence of carrier participation, the radiolabeled MORF showed increased accumulation in cells when incubated as the nanoparticle compared to the carrier-free nanoparticle and by as much as a factor of 11. Accumulation of the antisense MORF/streptavidin/tat nanoparticle was significantly higher than the sense MORF/streptavidin/tat nanoparticle as evidence of specific antisense targeting. CONCLUSIONS: The preparation of oligomer/carrier nanoparticles was greatly simplified over covalent conjugations by using streptavidin as a linker. Furthermore, our results suggest that the addition of streptavidin did not interfere with the cellular delivery function of the tat, polyarginine, or cholesterol carriers nor with the specific antisense mRNA binding function of the MORF oligomer.

Long circulating nanoparticles via adhesion on red blood cells: mechanism and extended circulation.
Chambers E, Mitragotri S.
Exp Biol Med (Maywood). 2007 Jul;232(7):958-66.
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Polymeric nanoparticles have long been sought after as carriers for systemic and targeted drug delivery. However, applications of nanoparticles are limited by their short in vivo circulation lifetimes. We report that by attaching polymeric nanoparticles to the surface of red blood cells, it is possible to dramatically improve their in vivo circulation lifetime. The particles remain in circulation as long as they remain attached to red blood cells. Particles eventually detach from red blood cells due to shear forces and cell-cell interactions and are subsequently cleared in the liver and spleen. Circulation of red blood cells themselves is not affected by particle attachment procedures. This manuscript reports an in depth analysis of the behavior of nanoparticles bound to red blood cells, especially their circulation characteristics, biodistribution, and mechanisms of clearance.

Continuous production of water dispersible carbon–iron nanocomposites by laser pyrolysis: Application as MRI contrasts.
Y. Lecontea Y, Veintemillas-Verdaguerb S, Moralesb MP, Costob R, Rodríguezc I, Bonvillea P, Bouchet-Fabrea B, Herlin-Boimea N.
J Colloid Interface Sci. 2007 Sep 15; 313(2):511-518.
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Carbon encapsulated iron/iron-oxide nanoparticles were obtained using laser pyrolysis method. The powders were processed to produce stable and biocompatible colloidal aqueous dispersions. The synthesis method consisted in the laser decomposition of an aerosol of ferrocene solution in toluene. This process generated, in a continuous way and in a single step, a nanocomposite formed by amorphous carbon nanoparticles of 50–100 nm size in which isolated iron based nanoparticles of 3–10 nm size are located. The effect of using different carriers and additives was explored in order to improve the efficiency of the process. The samples after purification by solid–liquid extraction with toluene, were oxidised in concentrated nitric acid solution of sodium chlorate, washed and finally ultrasonically dispersed in 1 mM tri-sodium citrate solutions. The dispersions obtained have hydrodynamic particle size less than 150 nm and are stable in the pH range of 2–11. Finally the shortening of the transversal relaxation time of water protons produced by the dispersed particles was studied in order to test the feasibility of these systems to be traced by magnetic resonance imaging techniques.

Strongly emissive individual DNA-encapsulated Ag nanoclusters as single-molecule fluorophores.
Vosch T, Antoku Y, Hsiang JC, Richards CI, Gonzalez JI, Dickson RM.
Proc Natl Acad Sci USA. 2007 Jul 31;104(31):12616-21.
[ expand abstract ]

The water-soluble, near-IR-emitting DNA-encapsulated silver nanocluster presented herein exhibits extremely bright and photostable emission on the single-molecule and bulk levels. The photophysics have been elucidated by intensity-dependent correlation analysis and suggest a heavy atom effect of silver that rapidly depopulates an excited dark level before quenching by oxygen, thereby conferring great photostability, very high single-molecule emission rates, and essentially no blinking on experimentally relevant time scales (0.1 to >1,000 ms). Strong antibunching is observed from these biocompatible species, which emit >10(9) photons before photobleaching. The significant dark-state quantum yield even enables bunching from the emissive state to be observed as a dip in the autocorrelation curve with only a single detector as the dark state precludes emission from the emissive level. These species represent significant improvements over existing dyes, and the nonpower law blinking kinetics suggest that these very small species may be alternatives to much larger and strongly intermittent semiconductor quantum dots.

Design and creation of new nanomaterials for therapeutic RNAi.
Baigude H, McCarroll J, Yang CS, Swain PM, Rana TM.
ACS Chem Biol. 2007 Apr 24;2(4):237-41.
[ expand abstract ]

RNA interference is an evolutionarily conserved gene-silencing phenomenon that shows great promise for developing new therapies. However, the development of small interfering RNA (siRNA)-based therapies needs to overcome two barriers and be able to (i) identify chemically stable and effective siRNA sequences and (ii) efficiently silence target genes with siRNA doses that will be clinically feasible in humans. Here, we report the design and creation of interfering nanoparticles (iNOPs) as new systemic gene-silencing agents. iNOPs have two subunits: (i) a well-defined functionalized lipid nanoparticle as a delivery agent and (ii) a chemically modified siRNA for sustained silencing in vivo. When we injected iNOPs containing only 1-5 mg kg(-1) siRNA into mice, an endogenous gene for apolipoprotein B (apoB) was silenced in liver, plasma levels of apoB decreased, and total plasma cholesterol was lowered. iNOP treatment was nontoxic and did not induce an immune response. Our results show that these iNOPs can silence disease-related endogenous genes in clinically acceptable and therapeutically affordable doses.

Preparation of poly(ethylene glycol)-modified poly(amido amine) dendrimers encapsulating gold nanoparticles and their heat-generating ability.
Haba Y, Kojima C, Harada A, Ura T, Horinaka H, Kono K.
Langmuir. 2007 May 8;23(10):5243-6.
[ expand abstract ]

Loading of HAuCl4 in poly(amido amine) G4 dendrimers having poly(ethylene glycol) (PEG) grafts at all chain ends and subsequent reduction with NaBH4 yielded PEG-modified dendrimers encapsulating gold nanoparticles (Au NPs) of ca. 2 nm diameter. The Au NPs held in the dendrimers were stable in aqueous solutions and dissolved readily, even after freeze-drying. Despite their small particle size, the heat-generating ability of Au NPs held in the dendrimer was comparable to that of widely used Au NPs with ca. 11 nm diameter under visible light irradiation. The observed excellent colloidal stability, high heat-generating ability and their biocompatible surface confirm that the PEG-modified dendrimers encapsulating Au NPs are a promising tool for photothermal therapy and imaging.

Surfactant-polymer nanoparticles: a novel platform for sustained and enhanced cellular delivery of water-soluble molecules.
Chavanpatil MD, Khdair A, Panyam J.
Pharm Res. 2007 Apr;24(4):803-10.
[ expand abstract ]

PURPOSE: Nanoparticles, drug carriers in the sub-micron size range, can enhance the therapeutic efficacy of encapsulated drug by increasing and sustaining the delivery of the drug inside the cell. However, the use of nanoparticles for small molecular weight, water-soluble drugs has been limited by poor drug encapsulation efficiency and rapid release of the encapsulated drug. Here we report enhanced cellular delivery of water-soluble molecules using novel AerosolOT (AOT)-alginate nanoparticles recently developed in our laboratory. MATERIALS AND METHODS: AOT-alginate nanoparticles were formulated using emulsion-crosslinking technology. Rhodamine and doxorubicin were used as model water-soluble molecules. Kinetics and mechanism of nanoparticle-mediated cellular drug delivery and therapeutic efficacy of nanoparticle-encapsulated doxorubicin were evaluated in two model breast cancer cell lines. RESULTS: AOT-alginate nanoparticles demonstrated sustained release of doxorubicin over a 15-day period in vitro. Cell culture studies indicated that nanoparticles enhanced the cellular delivery of rhodamine by about two-tenfold compared to drug in solution. Nanoparticle uptake into cells was dose-, time- and energy-dependent. Treatment with nanoparticles resulted in significantly higher cellular retention of drug than treatment with drug in solution. Cytotoxicity studies demonstrated that doxorubicin in nanoparticles resulted in significantly higher and more sustained cytotoxicity than drug in solution. CONCLUSIONS: AOT-alginate nanoparticles significantly enhance the cellular delivery of basic, water-soluble drugs. This translates into enhanced therapeutic efficacy for drugs like doxorubicin that have intracellular site of action. Based on these results, AOT-alginate nanoparticles appear to be suitable carriers for enhanced and sustained cellular delivery of basic, water-soluble drugs.

Synthesis and assessment of first-generation polyamidoamine dendrimer prodrugs to enhance the cellular permeability of P-gp substrates.
Najlah M, Freeman S, Attwood D, D'Emanuele A.
Bioconjug Chem. 2007 May-Jun;18(3):937-46.
[ expand abstract ]

The aim of this study is to evaluate the potential use of first-generation (G1) polyamidoamine (PAMAM) dendrimers as drug carriers to enhance the permeability, hence oral absorption, of drugs that are substrates for P-glycoprotein (P-gp) efflux transporters. G1 PAMAM dendrimer-based prodrugs of the water-insoluble P-gp substrate terfenadine (Ter) were synthesized using succinic acid (suc) or succinyl-diethylene glycol (suc-deg) as a linker/spacer (to yield G1-suc-Ter and G1-suc-deg-Ter, respectively). In addition, the permeability of G1-suc-deg-Ter was enhanced by attaching two lauroyl chains (L) to the dendrimer surface (L2-G1-suc-deg-Ter). All of the G1 dendrimer-terfenadine prodrugs were more hydrophilic than the parent drug, as evaluated by drug partitioning between 1-octanol and phosphate buffer at pH 7.4 (log K(app)). The influence of the dendrimer prodrugs on the integrity and viability of human Caucasian colon adenocarcinoma cells (Caco-2) was determined by measuring the transepithelial electrical resistance (TEER) and leakage of lactate dehydrogenase (LDH) enzyme, respectively. The LDH assay indicated that the dendrimer prodrugs had no impact on the viability of Caco-2 cells up to a concentration of 1 mM. However, the IC(50) of the prodrugs was lower than that of G1 PAMAM dendrimer because of the high toxicity of terfenadine. Measurements of the transport of dendrimer prodrugs across monolayers of Caco-2 cells showed an increase of the apparent permeability coefficient (P(app)) of terfenadine in both apical-to-basolateral (A --> B) and basolateral-to-apical (B --> A) directions after its conjugation to G1 PAMAM dendrimer. The A --> B P(app) of the dendrimer prodrugs was significantly greater than B --> A P(app). The surface-modified dendrimer prodrug L2-G1-suc-deg-Ter showed the highest A --> B permeability among the conjugates.

Cell-penetrating-peptide-coated nanoribbons for intracellular nanocarriers.
Lim YB, Lee E, Lee M.
Angew Chem Int Ed Engl. 2007;46(19):3475-8.
[ expand abstract ]

No abstract available (Citation link)

A cell nanoinjector based on carbon nanotubes.
Chen X, Kis A, Zettl A, Bertozzi CR.
Proc Natl Acad Sci U S A. 2007 May 15;104(20):8218-22.
[ expand abstract ]

Technologies for introducing molecules into living cells are vital for probing the physical properties and biochemical interactions that govern the cell's behavior. Here, we report the development of a nanoscale cell injection system (termed the nanoinjector) that uses carbon nanotubes to deliver cargo into cells. A single multiwalled carbon nanotube attached to an atomic force microscope (AFM) tip was functionalized with cargo via a disulfide-based linker. Penetration of cell membranes with this "nanoneedle" was controlled by the AFM. The following reductive cleavage of the disulfide bonds within the cell's interior resulted in the release of cargo inside the cells, after which the nanoneedle was retracted by AFM control. The capability of the nanoinjector was demonstrated by injection of protein-coated quantum dots into live human cells. Single-particle tracking was used to characterize the diffusion dynamics of injected quantum dots in the cytosol. This technique causes no discernible membrane or cell damage, and can deliver a discrete number of molecules to the cell's interior without the requirement of a carrier solvent.

Cell-penetrating quantum dots based on multivalent and endosome-disrupting surface coatings.
Duan H, Nie S.
J Am Chem Soc. 2007 Mar 21;129(11):3333-8.
[ expand abstract ]

We report the development of cell-penetrating quantum dots (QDs) based on the use of multivalent and endosome-disrupting (endosomolytic) surface coatings. Hyperbranched copolymer ligands such as polyethylene glycol (PEG) grafted polyethylenimine (PEI-g-PEG) are found to encapsulate and solubilize luminescent quantum dots through direct ligand-exchange reactions. Because of the positive charges and a "proton sponge effect" associated with multivalent amine groups, this class of ligand-exchanged QDs is able to penetrate cell membranes and is also able to disrupt endosomal organelles in living cells. The grafted PEG segment is essential for reducing the cytotoxicity of PEI as well as for improving the overall nanoparticle stability and biocompatibility. In comparison with previous QDs encapsulated with amphiphilic polymers, the cell-penetrating QDs are smaller in size and are considerably more stable in acidic environments. Cellular uptake and imaging studies reveal that the number of PEG grafts per PEI molecule has a pronounced effect on the intracellular pathways of internalized QDs. In particular, QDs coated with PEI-g-PEG2 are rapidly internalized by endocytosis, and are initially stored in vesicles, followed by slow endosomal escape and release into the cytoplasm. These insights are important toward the design and development of nanoparticle agents for intracellular imaging and therapeutic applications.

Live dynamic imaging of caveolae pumping targeted antibody rapidly and specifically across endothelium in the lung.
Oh P, Borgström P, Witkiewicz H, Li Y, Borgström BJ, Chrastina A, Iwata K, Zinn KR, Baldwin R, Testa JE, Schnitzer JE.
Nat Biotechnol. 2007 Mar;25(3):327-37.
[ expand abstract ]

How effectively and quickly endothelial caveolae can transcytose in vivo is unknown, yet critical for understanding their function and potential clinical utility. Here we use quantitative proteomics to identify aminopeptidase P (APP) concentrated in caveolae of lung endothelium. Electron microscopy confirms this and shows that APP antibody targets nanoparticles to caveolae. Dynamic intravital fluorescence microscopy reveals that targeted caveolae operate effectively as pumps, moving antibody within seconds from blood across endothelium into lung tissue, even against a concentration gradient. This active transcytosis requires normal caveolin-1 expression. Whole body gamma-scintigraphic imaging shows rapid, specific delivery into lung well beyond that achieved by standard vascular targeting. This caveolar trafficking in vivo may underscore a key physiological mechanism for selective transvascular exchange and may provide an enhanced delivery system for imaging agents, drugs, gene-therapy vectors and nanomedicines. 'In vivo proteomic imaging' as described here integrates organellar proteomics with multiple imaging techniques to identify an accessible target space that includes the transvascular pumping space of the caveola.

A Highly Selective, One-Pot Purification Method for Single-Walled Carbon Nanotubes.
Wang Y, Shan H, Hauge RH, Pasquali M, Smalley RE.
J Phys Chem B Condens Matter Mater Surf Interfaces Biophys. 2007 Feb 15;111(6):1249-1252.
[ expand abstract ]

We report on a one-pot, highly selective chemistry to remove residual catalysts from single-walled carbon nanotubes (SWNTs). The impurities, initially present at approximately 35 wt % and mostly as carbon-coated iron nanoparticles, can be driven below 5 wt % with nearly no loss of SWNTs. The carbon-coated iron impurities are dissolved simply by reacting with an aqueous mixture of H2O2 and HCl at 40-70 degrees C for 4-8 h. This purification combines two known reactions involving H2O2 and HCl, respectively; however, by combining these two typically inefficient reactions into a one-pot reaction, the new process is surprisingly selective toward the removal of the metal impurities. This high selectivity derives from the proximity effect of the iron-catalyzed Fenton chemistry. At pH approximately 1-3, iron is dissolved upon exposure, avoiding the otherwise aggressive iron-catalyzed digestion of SWNTs by H2O2. This extremely simple and selective chemistry offers a "green" and scalable process to purify carbon nanotube materials.

Multicomponent Nanoparticles via Self-Assembly with Cross-Linked Block Copolymer Surfactants.
Kim BS, Taton TA.
Langmuir. 2007 Feb 13;23(4):2198-202.
[ expand abstract ]

We describe a simple and versatile protocol to prepare water-soluble multifunctional nanostructures by encapsulation of different nanoparticles in shell cross-linked, block copolymer micelles. This method permits simultaneous incorporation of different nanoparticle properties within a nanoscale micellar container. We have demonstrated the co-encapsulation of magnetic (gamma-Fe2O3 and Fe3O4), semiconductor (CdSe/ZnS), and metal (Au) nanoparticles in different combinations to form multicomponent micelles that retain the precursor particles' distinct properties. Because these multifunctional hybrid nanostructures spontaneously assemble from solution by simultaneous desolvation of nanoparticles and amphiphilic block copolymer components, we anticipate that this can be used as a general protocol for preparing multifunctional nanostructures without explicit multimaterial synthesis or surface functionalization of nanoparticles.

Functionalization of monodisperse magnetic nanoparticles.
Lattuada M, Hatton TA.
Langmuir. 2007 Feb 13;23(4):2158-68.
[ expand abstract ]

We report a new strategy for the preparation of monodisperse, water-soluble magnetic nanoparticles. Oleic acid-stabilized magnetic nanocrystals were prepared by the organic synthesis route proposed by Sun et al. (J. Am. Chem. Soc. 2004, 126, 273.), with size control obtained via seeded-mediated growth. The oleic groups initially present on the nanoparticle surfaces were replaced via ligand exchange reactions with various capping agents bearing reactive hydroxyl moieties. These hydroxyl groups were (i) exploited to initiate ring opening polymerization (ROP) of polylactic acid from the nanoparticle surfaces and (ii) esterified by acylation to permit the addition of alkyl halide moieties to transform the nanoparticle surfaces into macroinitiators for atom transfer radical polymerization (ATRP). By appropriate selection of the ligand properties, the nanoparticle surfaces can be polymerized in various solvents, providing an opportunity for the growth of a wide variety of water-soluble polymers and polylectrolyte brushes (both cationic and anionic) from the nanoparticle surfaces. The nanoparticles were characterized by Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), electron microscopy, and light scattering. Light scattering measurements indicate that the nanoparticles are mostly present as individual nonclustered units in water. With pH-responsive polymers grown on the nanoparticle surfaces, reversible aggregation of nanoparticles could be induced by suitable swings in the pH between the stable and unstable regions.

Highly Luminescent Eu(3+) Chelate Nanoparticles Prepared by a Reprecipitation-Encapsulation Method.
Peng H, Wu C, Jiang Y, Huang S, McNeill J.
Langmuir. 2007 Feb 13;23(4):1591-1595.
[ expand abstract ]

Aqueous suspensions of highly luminescent Eu3+ chelate nanoparticles are prepared by a novel reprecipitation-encapsulation method. An alkyl alkoxysilane encapsulation agent is included during the nanoparticle formation process, forming a nanoparticle encapsulation layer that inhibits aggregation as evidenced by UV-vis spectroscopy and atomic force microscopy. In addition, the encapsulated nanoparticles exhibit a small size (10 nm), intense luminescence, and excellent photostability. We estimate that the molar extinction coefficients of the approximately 10 nm particles are approximately 5.0 x 107 M-1 cm-1 with a luminescence quantum yield of 6%, indicating a luminescence brightness many times larger than that of conventional fluorescent dyes and comparable to that of colloidal semiconductor quantum dots. The small size, high brightness, highly red-shifted luminescence, and long luminescence lifetimes of the nanoparticles are of interest for luminescence labeling and sensing applications.

Synthesis, Stability, and Cellular Internalization of Gold Nanoparticles Containing Mixed Peptide-Poly(ethylene glycol) Monolayers.
Liu Y, Shipton MK, Ryan J, Kaufman ED, Franzen S, Feldheim DL.
Anal Chem. 2007 Feb 9; [Epub ahead of print].
[ expand abstract ]

Gold nanoparticles have shown great promise as therapeutics, therapeutic delivery vectors, and intracellular imaging agents. For many biomedical applications, selective cell and nuclear targeting are desirable, and these remain a significant practical challenge in the use of nanoparticles in vivo. This challenge is being addressed by the incorporation of cell-targeting peptides or antibodies onto the nanoparticle surface, modifications that frequently compromise nanoparticle stability in high ionic strength biological media. We describe herein the assembly of poly(ethylene glycol) (PEG) and mixed peptide/PEG monolayers on gold nanoparticle surfaces. The stability of the resulting bioconjugates in high ionic strength media was characterized as a function of nanoparticle size, PEG length, and monolayer composition. In total, three different thiol-modified PEGs (average molecular weight (MW), 900, 1500, and 5000 g mol-1), four particle diameters (10, 20, 30, and 60 nm), and two cell-targeting peptides were explored. We found that nanoparticle stability increased with increasing PEG length, decreasing nanoparticle diameter, and increasing PEG mole fraction. The order of assembly also played a role in nanoparticle stability. Mixed monolayers prepared via the sequential addition of PEG followed by peptide were more stable than particles prepared via simultaneous co-adsorption. Finally, the ability of nanoparticles modified with mixed PEG/RME (RME = receptor-mediated endocytosis) peptide monolayers to target the cytoplasm of HeLa cells was quantified using inductively coupled plasma optical emission spectrometry (ICP-OES). Although it was anticipated that the MW 5000 g mol-1 PEG would sterically block peptides from access to the cell membrane compared to the MW 900 PEG, nanoparticles modified with mixed peptide/PEG 5000 monolayers were internalized as efficiently as nanoparticles containing mixed peptide/PEG 900 monolayers. These studies can provide useful cues in the assembly of stable peptide/gold nanoparticle bioconjugates capable of being internalized into cells.

Biopolymer-based materials: the nanoscale components and their hierarchical assembly.
Payne GF.
Curr Opin Chem Biol. 2007 Feb 9; [Epub ahead of print].
[ expand abstract ]

Protein and nucleic acid biopolymers are well appreciated for their high-performance capabilities for molecular recognition, catalysis and information storage. Increasingly, these biopolymers are being examined for materials applications. Less tractable are polysaccharides and polymers of phenols, which, despite being nature's most abundant macromolecules, remain largely ignored for advanced materials applications. In our opinion, it seems certain that biology will contribute two major capabilities for materials biofabrication - the means to generate biopolymeric components with nanoscale precision, and the mechanisms for the hierarchical assembly of nanocomponents. These capabilities will enable unprecedented control of materials structure and provide exciting opportunities at the convergence of molecular biology and macromolecular science.

Dendrimers as multi-purpose nanodevices for oncology drug delivery and diagnostic imaging.
Tomalia DA, Reyna LA, Svenson S.
Biochem Soc Trans. 2007 Feb;35(Pt 1):61-7.
[ expand abstract ]

Dendrimers are routinely synthesized as tuneable nanostructures that may be designed and regulated as a function of their size, shape, surface chemistry and interior void space. They are obtained with structural control approaching that of traditional biomacromolecules such as DNA/RNA or proteins and are distinguished by their precise nanoscale scaffolding and nanocontainer properties. As such, these important properties are expected to play an important role in the emerging field of nanomedicine. This review will describe progress on the use of these features for both targeted diagnostic imaging and drug-delivery applications. Recent efforts have focused on the synthesis and pre-clinical evaluation of a multipurpose STARBURST(R) PAMAM (polyamidoamine) dendrimer prototype that exhibits properties suitable for use as: (i) targeted, diagnostic MRI (magnetic resonance imaging)/NIR (near-IR) contrast agents, (ii) and/or for controlled delivery of cancer therapies. Special emphasis will be placed on the lead candidate, namely [core: 1,4-diaminobutane; G (generation)=4.5], [dendri-PAMAM(CO(2)Na)(64)]. This dendritic nanostructure (i.e. approximately 5.0 nm diameter) was selected on the basis of a very favourable biocompatibility profile [The Nanotechnology Characterization Laboratory (NCL), an affiliate of the National Cancer Institute (NCI), has completed extensive in vitro studies on the lead compound and have found it to be very benign, non-immunogenic and highly biocompatible], the expectation that it will exhibit desirable mammalian kidney excretion properties and demonstrated targeting features.

Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles.
Cedervall T, Lynch I, Lindman S, Berggard T, Thulin E, Nilsson H, Dawson KA, Linse S.
Proc Natl Acad Sci USA. 2007 Jan 31; [Epub ahead of print].
[ expand abstract ]

Due to their small size, nanoparticles have distinct properties compared with the bulk form of the same materials. These properties are rapidly revolutionizing many areas of medicine and technology. Despite the remarkable speed of development of nanoscience, relatively little is known about the interaction of nanoscale objects with living systems. In a biological fluid, proteins associate with nanoparticles, and the amount and presentation of the proteins on the surface of the particles leads to an in vivo response. Proteins compete for the nanoparticle "surface," leading to a protein "corona" that largely defines the biological identity of the particle. Thus, knowledge of rates, affinities, and stoichiometries of protein association with, and dissociation from, nanoparticles is important for understanding the nature of the particle surface seen by the functional machinery of cells. Here we develop approaches to study these parameters and apply them to plasma and simple model systems, albumin and fibrinogen. A series of copolymer nanoparticles are used with variation of size and composition (hydrophobicity). We show that isothermal titration calorimetry is suitable for studying the affinity and stoichiometry of protein binding to nanoparticles. We determine the rates of protein association and dissociation using surface plasmon resonance technology with nanoparticles that are thiol-linked to gold, and through size exclusion chromatography of protein-nanoparticle mixtures. This method is less perturbing than centrifugation, and is developed into a systematic methodology to isolate nanoparticle-associated proteins. The kinetic and equilibrium binding properties depend on protein identity as well as particle surface characteristics and size.

Biomolecule-nanoparticle hybrids as functional units for nanobiotechnology.
Baron R, Willner B, Willner I.
Chem Commun (Camb). 2007 Jan 28;(4):323-32.
[ expand abstract ]

Biomolecule-metal or semiconductor nanoparticle (NP) hybrid systems combine the recognition and catalytic properties of biomolecules with the unique electronic and optical properties of NPs. This enables the application of the hybrid systems in developing new electronic and optical biosensors, to synthesize nanowires and nanocircuits, and to fabricate new devices. Metal NPs are employed as nano-connectors that activate redox enzymes, and they act as electrical or optical labels for biorecognition events. Similarly, semiconductor NPs act as optical probes for biorecognition processes. Double-stranded DNA or protein chains that are modified with metallic nanoclusters act as templates for the synthesis of metallic nanowires. The nanowires are used as building blocks to assemble nano-devices such as a transistor or a nanotransporter.

Nanotechnological applications in medicine.
Caruthers SD, Wickline SA, Lanza GM.
Curr Opin Biotechnol. 2007 Jan 23; [Epub ahead of print].
[ expand abstract ]

Nanotechnology-based tools and techniques are rapidly emerging in the fields of medical imaging and targeted drug delivery. Employing constructs such as dendrimers, liposomes, nanoshells, nanotubes, emulsions and quantum dots, these advances lead toward the concept of personalized medicine and the potential for very early, even pre-symptomatic, diagnoses coupled with highly-effective targeted therapy. Highlighting clinically available and preclinical applications, this review explores the opportunities and issues surrounding nanomedicine.

Fullerene-Derivatized Amino Acids: Synthesis, Characterization, Antioxidant Properties, and Solid-Phase Peptide Synthesis.
Yang J, Alemany LB, Driver J, Hartgerink JD, Barron AR.
Chemistry. 2007 Jan 19; [Epub ahead of print].
[ expand abstract ]

A series of [60]fullerene-substituted phenylalanine (Baa) and lysine derivatives have been prepared by the condensation of 1,2-(4'-oxocyclohexano)fullerene with the appropriately protected (4-amino)phenylalanine and lysine, respectively. Conversion of the imine to the corresponding amine is achieved by di-acid catalyzed hydroboration. The reduction of the imine is not accompanied by hydroboration of the fullerene cage. The [70]fullerene phenylalanine derivative has also been prepared as have the di-amino acid derivatives. The compounds were characterized by MALDI-TOF mass spectrometry, UV/Vis spectroscopy, and cyclic voltammetry. (1)H and (13)C NMR spectroscopy allowed the observation of diastereomers. Fullerene-substituted peptides may be synthesized on relatively large scale by solid-phase peptide synthesis. The presence of the C(60)-substituted amino acid in a peptide has a significant effect on the secondary structures and self-assembly properties of peptides as compared to the native peptide. The antioxidant assay of Baa and a Baa-derived anionic peptide was determined to be significantly more potent than Trolox.

Synthesis and temperature response analysis of magnetic-hydrogel nanocomposites.
Frimpong RA, Fraser S, Zach Hilt J.
J Biomed Mater Res A. 2007 Jan;80(1):1-6.
[ expand abstract ]

Magnetically responsive hydrogel networks based on composites of magnetic nanoparticles and temperature responsive hydrogels were developed. These systems show great promise as active components of microscale and nanoscale devices and are expected to have a wide applicability in various biomedical applications. Specifically, nanocomposite hydrogel systems based on the temperature sensitive N-isopropylacrylamide hydrogels crosslinked with ethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, and poly(ethylene glycol) 400 dimethacrylate (PEG400DMA) were synthesized and characterized. The composite systems were synthesized by UV free-radical polymerization. Iron oxide magnetic nanoparticles were incorporated into the hydrogel systems by polymerizing mixtures of the nanoparticles and monomer solutions. The swelling response of these composite systems to different crosslinking molecular weights, temperature, and the effect of the presence of the magnetic nanoparticles were examined.

Quenching of photoluminescence in conjugates of quantum dots and single-walled carbon nanotube.
Biju V, Itoh T, Baba Y, Ishikawa M.
J Phys Chem B Condens Matter Mater Surf Interfaces Biophys.
2006 Dec 28;110(51):26068-74.
[ expand abstract ]

Development of quantum dot (QD) based device components requires controlled integration of QDs into different photonic and electronic materials. In this regard, introduction of methods for regular arrangement of QDs and investigation of properties of QD-based assemblies are important. In the current work we report (1) controlled conjugation of CdSe-ZnS QDs to sidewall-functionalized single-walled carbon nanotube (SWCNT) templates (2) and the effect of conjugation of QDs to SWCNT on the photoluminescence (PL) properties of QDs. We identified that PL intensity and lifetime of QDs are considerably reduced after conjugation to SWCNT. The origin of the quenching of the PL intensity and lifetime was discussed in terms of Forster resonance energy transfer (FRET). FRET involves nonradiative transfer of energy from a photoexcited QD (energy donor) to a nearby SWCNT (energy acceptor) in the ground state. This was examined by varying the density of QDs on SWCNT and conjugating smaller and bigger QDs to the same SWCNT. We estimated the FRET efficiency in QD-SWCNT conjugates from the quenching of the PL intensity and lifetime and identified that FRET is independent of the density and type of QDs on SWCNT but inherent to QD-SWCNT conjugates.

Template synthesized molecularly imprinted polymer nanotube membranes for chemical separations.
Wang HJ, Zhou WH, Yin XF, Zhuang ZX, Yang HH, Wang XR.
J Am Chem Soc. 2006 Dec 20;128(50):15954-5.
[ expand abstract ]

No abstract available

Nanoparticle-enzyme hybrid systems for nanobiotechnology.
Willner I, Basnar B, Willner B.
FEBS J. 2006 Dec 20; [Epub ahead of print].
[ expand abstract ]

Biomolecule-nanoparticle (NP) [or quantum-dot (QD)] hybrid systems combine the recognition and biocatalytic properties of biomolecules with the unique electronic, optical, and catalytic features of NPs and yield composite materials with new functionalities. The biomolecule-NP hybrid systems allow the development of new biosensors, the synthesis of metallic nanowires, and the fabrication of nanostructured patterns of metallic or magnetic NPs on surfaces. These advances in nanobiotechnology are exemplified by the development of amperometric glucose sensors by the electrical contacting of redox enzymes by means of AuNPs, and the design of an optical glucose sensor by the biocatalytic growth of AuNPs. The biocatalytic growth of metallic NPs is used to fabricate Au and Ag nanowires on surfaces. The fluorescence properties of semiconductor QDs are used to develop competitive maltose biosensors and to probe the biocatalytic functions of proteases. Similarly, semiconductor NPs, associated with electrodes, are used to photoactivate bioelectrocatalytic cascades while generating photocurrents.

Adsorption and hybridization of oligonucleotides on mercaptoacetic acid-capped CdSe/ZnS quantum dots and quantum dot-oligonucleotide conjugates.
Algar WR, Krull UJ.
Langmuir. 2006 Dec 19;22(26):11346-52.
[ expand abstract ]

Interest in the unique optical properties of quantum dots (QDs) has resulted in the development QD-bioconjugates for imaging and diagnostics. Although these applications are numerous, considerably less is known about the interactions between QDs and biomolecules. In this work, we describe hydrogen-bonding interactions between oligonucleotides and CdSe/ZnS quantum dots capped with mercaptoacetic acid ligands. The strength of the interactions can be modulated by changes in the pH and ionic strength, the addition of formamide, and differences between ssDNA and dsDNA. Fluorescence resonance energy transfer experiments have shown that conjugated oligonucleotides adopt a conformation that lies across the surface of the QD. The hydrogen-bonding interactions also affect the kinetics of hybridization with QD-DNA conjugates and the thermal stability of QD-conjugated dsDNA. The former is analogous to conventional solid-phase hybridization, where stronger oligonucleotide adsorption leads to faster kinetics. With respect to the latter, interactions with the QD surface can sharpen the melt transition and alter the melt temperature of dsDNA. These effects are largely absent when adsorptive interactions are minimized.

Arylthiolate-protected silver quantum dots.
Branham MR, Douglas AD, Mills AJ, Tracy JB, White PS, Murray RW.
Langmuir. 2006 Dec 19;22(26):11376-83.
[ expand abstract ]

This paper describes a new, organic-soluble 4-tert-butylbenzyl mercaptan (BBT) monolayer-protected silver cluster (AgBBT MPC) as the first example of a dissolved silver nanoparticle that exhibits quantized one-electron double layer charging (QDL) voltammetry. Polydisperse AgBBT MPCs made by two different synthetic protocols, but with similar average core diameters (2.1 nm), exhibit sharply differing electrochemistry and optical absorbance spectra. A two-phase procedure (organic/aqueous, termed Prep A-AgBBT) produced MPCs exhibiting a 475 nm surface plasmon absorbance and QDL voltammetry. Neither property was seen for MPCs made by a single-phase procedure, termed Prep B-AgBBT. The difference is thought to reflect poor passivation to oxide formation in the latter Prep B procedure, which is supported by X-ray photoelectron spectroscopy results. Thermogravimetry, mass spectra, and electrochemistry results suggest an average stoichiometric formula of Ag140BBT53, but transmission electron microscopy shows that the products are also polydisperse and include polycrystalline aggregates. Dry, cast films of both Ag MPC preparations on interdigitated array electrodes exhibit low electron hopping conductivity, compared to Au MPCs.

Optimization of the methods for introduction of amine groups onto the silica nanoparticle surface.
Liu S, Zhang HL, Liu TC, Liu B, Cao YC, Huang ZL, Zhao YD, Luo QM.
J Biomed Mater Res A. 2006 Dec 19; [Epub ahead of print].
[ expand abstract ]

The luminescent silica nanoparticle has attracted the researchers' concentration in bioanalysis recently. Its extensive application is based on the immobilization of various biomolecules such as deoxyribonucleic acid, antibody, and so forth onto the surface. By comparing different introduction methods of amine groups, it was confirmed that the "two-step" route is more preferable by adding tetraethyl orthosilicate and 3-aminopropyl-(triethoxyl)silane in sequence, to attain ideal amine-modified silica nanoparticles. On this basis, carboxyl groups were derived from amine groups on the nanoparticle surface and then were activated by 1-ethyl-3-3-(3-dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxy-succinimide. Finally, mouse monoclonal antihuman CD71 antibody (McAb CD71) and transferrin were effectively linked with the carboxyl groups and successfully labeled the receptors in the membrane of fibroblast cells, respectively.

Maximizing DNA loading on a range of gold nanoparticle sizes.
Hurst SJ, Lytton-Jean AK, Mirkin CA.
Anal Chem. 2006 Dec 15;78(24):8313-8.
[ expand abstract ]

We have investigated the variables that influence DNA coverage on gold nanoparticles. The effects of salt concentration, spacer composition, nanoparticle size, and degree of sonication have been evaluated. Maximum loading was obtained by salt aging the nanoparticles to approximately 0.7 M NaCl in the presence of DNA containing a poly(ethylene glycol) spacer. In addition, DNA loading was substantially increased by sonicating the nanoparticles during the surface loading process. Last, nanoparticles up to 250 nm in diameter were found have approximately 2 orders of magnitude higher DNA loading than smaller (13-30 nm) nanoparticles, a consequence of their larger surface area. Stable large particles are attractive for a variety of biodiagnostic assays.

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Development of High Magnetization Fe(3)O(4)/Polystyrene/Silica Nanospheres via Combined Miniemulsion/Emulsion Polymerization.
Xu H, Cui L, Tong N, Gu H.
J Am Chem Soc. 2006 Dec 13;128(49):15582-3.
[ expand abstract ]

Monodispersed, hydrophilic, superparamagnetic magnetic nanospheres with a high fraction of magnetite were synthesized by combining modified miniemulsion/emulsion polymerization and sol-gel technique for the first time. The surface of the nanospheres was coated by a silica layer with controlled thickness. Transmission electron microscopy experimental results showed well-proportioned, equal-sized, magnetite/polystyrene (Fe3O4/PS) nanospheres with a thin silica shell. Based on the TGA data, the fraction of magnetite in the Fe3O4/PS nanospheres core was estimated to be 80 wt %. Magnetization measurements indicated that the superparamagnetic nature of the nanospheres had high saturation magnetization of 40 emu/g at 300 K. The procedures of the novel synthesis are described in detail. Also discussed are the mechanisms of the novel combined miniemulsion/emulsion polymerization processes.

Quantitative measurement and control of oxygen levels in microfluidic poly(dimethylsiloxane) bioreactors during cell culture.
Mehta G, Mehta K, Sud D, Song JW, Bersano-Begey T, Futai N, Heo YS, Mycek MA, Linderman JJ, Takayama S.
Biomed Microdevices. 2006 Dec 12; [Epub ahead of print].
[ expand abstract ]

Microfluidic bioreactors fabricated from highly gas-permeable poly(dimethylsiloxane) (PDMS) materials have been observed, somewhat unexpectedly, to give rise to heterogeneous long term responses along the length of a perfused mammalian cell culture channel, reminiscent of physiologic tissue zonation that arises at least in part due to oxygen gradients. To develop a more quantitative understanding and enable better control of the physical-chemical mechanisms underlying cell biological events in such PDMS reactors, dissolved oxygen concentrations in the channel system were quantified in real time using fluorescence intensity and lifetime imaging of an oxygen sensitive dye, ruthenium tris(2,2'-dipyridyl) dichloride hexahydrate (RTDP). The data indicate that despite oxygen diffusion through PDMS, uptake of oxygen by cells inside the perfused PDMS microchannels induces an axial oxygen concentration gradient, with lower levels recorded in downstream regions. The oxygen concentration gradient generated by a balance of cellular uptake, convective transport by media flow, and permeation through PDMS in our devices ranged from 0.0003 (mg/l)/mm to 0.7 (mg/l)/mm. The existence of such steep gradients induced by cellular uptake can have important biological consequences. Results are consistent with our mathematical model and give insight into the conditions under which flux of oxygen through PDMS into the microchannels will or will not contribute significantly to oxygen delivery to cells and also provide a design tool to manipulate and control oxygen for cell culture and device engineering. The combination of computerized microfluidics, in situ oxygen sensing, and mathematical models opens new windows for microphysiologic studies utilizing oxygen gradients and low oxygen tensions.

Micropatterned surfaces for controlling cell adhesion and rolling under flow.
Nalayanda DD, Kalukanimuttam M, Schmidtke DW.
Biomed Microdevices. 2006 Dec 12; [Epub ahead of print].
[ expand abstract ]

Cell adhesion and rolling on the vascular wall is critical to both inflammation and thrombosis. In this study we demonstrate the feasibility of using microfluidic patterning for controlling cell adhesion and rolling under physiological flow conditions. By controlling the width of the lines (50-1000 mum) and the spacing between them (50-100 mum) we were able to fabricate surfaces with well-defined patterns of adhesion molecules. We demonstrate the versatility of this technique by patterning surfaces with 3 different adhesion molecules (P-selectin, E-selectin, and von Willebrand Factor) and controlling the adhesion and rolling of three different cell types (neutrophils, Chinese Hamster Ovary cells, and platelets). By varying the concentration of the incubating solution we could control the surface ligand density and hence the cell rolling velocity. Finally by patterning surfaces with both P-selectin and von Willebrand Factor we could control the rolling of both leukocytes and platelets simultaneously. The technique described in this paper provides and effective and inexpensive way to fabricate patterned surfaces for use in cell rolling assays under physiologic flow conditions.

Truncated forms of viral VP2 proteins fused to EGFP assemble into fluorescent parvovirus-like particles.
Gilbert L, Toivola J, Valilehto O, Saloniemi T, Cunningham C, White D, Makela AR, Korhonen E, Vuento M, Oker-Blom C.
J Nanobiotechnology. 2006 Dec 8;4(1):13 [Epub ahead of print].
[ expand abstract ]

ABSTRACT: Fluorescence correlation spectroscopy (FCS) monitors random movements of fluorescent molecules in solution, giving information about the number and the size of for example nano-particles. The canine parvovirus VP2 structural protein as well as N-terminal deletion mutants of VP2 (-14, -23, and -40 amino acids) were fused to the C-terminus of the enhanced green fluorescent protein (EGFP). The proteins were produced in insect cells, purified, and analyzed by western blotting, confocal and electron microscopy as well as FCS. The non-truncated form, EGFP-VP2, diffused with a hydrodynamic radius of 17 nm, whereas the fluorescent mutants truncated by 14, 23 and 40 amino acids showed hydrodynamic radii of 7, 20 and 14 nm, respectively. These results show that the non-truncated EGFP-VP2 fusion protein and the EGFP-VP2 constructs truncated by 23 and by as much as 40 amino acids were able to form virus-like particles (VLPs). The fluorescent VLP, harbouring VP2 truncated by 23 amino acids, showed a somewhat larger hydrodynamic radius compared to the non-truncated EGFP-VP2. In contrast, the construct containing EGFP-VP2 truncated by 14 amino acids was not able to assemble into VLP resembling structures. Formation of capsid structures was confirmed by confocal and electron microscopy. The number of fluorescent fusion protein molecules present within the different VLPs was determined by FCS. In conclusion, FCS provides a novel strategy to analyze virus assembly and gives valuable structural information for strategic development of parvovirus-like particles.

Aggregated CdS Quantum Dots: Host of Biomolecular Ligands.
Narayanan SS, Pal SK.
J Phys Chem B Condens Matter Mater Surf Interfaces Biophys. 2006 Dec 7;110(48):24403-9.
[ expand abstract ]

In this contribution, we have studied structural and photophysical properties of aggregated CdS quantum dots (QDs) capped with 2-mercaptoethanol in aqueous medium. The hydrodynamic diameter of the nanostructures in aqueous solution was found to be approximately 160 nm with the dynamic light scattering (DLS) technique, which is in close agreement with atomic force microscopy (AFM) studies (diameter approximately 150 nm). However, the UV-vis absorption spectroscopy, powder X-ray diffraction (XRD), and transmission electron microscopy (TEM) studies confirm the average particle size (QD) in the nanoaggregate to be 4.0 +/- 0.5 nm. The steady-state and time-resolved photoluminescence studies on the QDs further confirm preservation of electronic band structure of the QDs in the nanoaggregate. To study the nature of the nanoaggregate we have used small fluorescent probes, which are widely used as biomolecular ligands (2,6-p-toluidinonaphthalene sulfonate (TNS) and Oxazine 1), and found the pores of the aggregate to be hydrophobic in nature. The significantly large spectral overlap of the host quantum dots (donor) with that of the guest fluorescent probe Oxazine 1 (acceptor) allows us to carry out Forster resonance energy transfer (FRET) studies to estimate average donor-acceptor distance in the nanostructure, found to be approximately 25 A. The quantum dot aggregate and the characterization techniques reported here could have implications in the future application of the QD-nanoaggregate as host of small ligand molecules of biological interest.

Compact, high performance surface plasmon resonance imaging system.
Chinowsky TM, Grow MS, Johnston KS, Nelson K, Edwards T, Fu E, Yager P.
Biosens Bioelectron. 2006 Dec 4; [Epub ahead of print].
[ expand abstract ]

We report the construction and characterization of a new compact surface plasmon resonance imaging instrument. Surface plasmon resonance imaging is a versatile technique for detection, quantification and visualization of biomolecular binding events which have spatial structure. The imager uses a folded light path, wide-field optics and a tilted detector to implement a high performance optical system in a volume 7in.x4in.x2in. A bright diode light source and an image detector with fast frame rate and integrated digital signal processor enable real-time averaging of multiple images for improved signal-to-noise ratio. Operating angle of the imager is adjusted by linear translation of the light source. Imager performance is illustrated using resolution test targets, refractive index test solutions, and competition assays for the antiepileptic drug phenytoin. Microfluidic flowcells are used to enable simultaneous assay of three sample streams. Noise level of refractive index measurements was found to decrease proportional to the square root of the number of pixels averaged, reaching approximately 5x10(-7) refractive index units root-mean-square for 160x120 pixels image regions imaged for 1s. The simple, compact construction and high performance of the imager will allow the device to be readily applied to a wide range of applications.

Electrohydrodynamic Generation and Delivery of Monodisperse Picoliter Droplets Using a Poly(dimethylsiloxane) Microchip.
Kim SJ, Song YA, Skipper PL, Han J.
Anal Chem. 2006 Dec 1;78(23):8011-9.
[ expand abstract ]

We developed a drop-on-demand microdroplet generator for the discrete dispensing of biosamples into a bioanalytical unit. This disposable PDMS microfluidic device can generate monodisperse droplets of picoliter volume directly out of a plane sidewall of the microfluidic chip by an electrohydrodynamic mechanism. The droplet generation was accomplished without using either an inserted capillary or a monolithically built-in tip. The minimum droplet volume was approximately 4 pL, and the droplet generation was repeatable and stable for at least 30 min, with a typical variation of less than 2.0% of drop size. The Taylor cone, which is usually observed in electrospray, was suppressed by controlling the surface wetting property of the PDMS device as well as the surface tension of the sample liquids. A modification of the channel geometry right before the opening of the microchannel also enhanced the continuous droplet generation without applying any external pumping. A simple numerical simulation of the droplet generation verified the importance of controlling the surface wetting conditions for the droplet formation. Our microdroplet generator can be effectively applied to a direct interface of a microfluidic chip to a biosensing unit, such as AMS, MALDI-MS or protein microarray-type biochips.

Separation of acidic and basic proteins by nanoparticle-filled capillary electrophoresis.
Yu CJ, Su CL, Tseng WL.
Anal Chem. 2006 Dec 1;78(23):8004-10.
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We present the first example of the analysis of acidic and basic proteins by nanoparticle-filled capillary electrophoresis. Compared to the didodecyldimethylammonium bromide (DDAB)-coated capillary, the DDAB-capped gold nanoparticles (AuNPs) as pseudostationary phase were found to form more stable coating on the capillary wall, thus leading to greater separation efficiency and high reproducibility. In addition to their advantages for protein separation, DDAB-capped AuNPs can generate high reversed electroosmotic flow, which is 75% greater than DDAB at pH 3.5. To allow strong interactions with proteins, the AuNPs were modified with poly(ethylene oxide) via noncovalent bonding to form gold nanoparticles/polymer composites (AuNPPs). Using a capillary dynamically coated with DDAB-capped AuNPs and filled with AuNPPs under acidic conditions (10 mM phosphate, pH 3.5), we have demonstrated the separation of acidic and basic proteins with peak efficiencies ranging from 71 000 to 1 007 000 plates/m and relative standard deviations of migration time less than 0.6%. Additionally, the proposed method has been applied to the analyses of biological samples, including saliva, red blood cells, and plasma. With simplicity, high resolving power, and high reproducibility, the proposed method has shown great potential for proteomics applications and clinical diagnosis.

Combined microfluidic-micromagnetic separation of living cells in continuous flow.
Xia N, Hunt TP, Mayers BT, Alsberg E, Whitesides GM, Westervelt RM, Ingber DE.
Biomed Microdevices. 2006 Dec;8(4):299-308.
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This paper describes a miniaturized, integrated, microfluidic device that can pull molecules and living cells bound to magnetic particles from one laminar flow path to another by applying a local magnetic field gradient, and thus selectively remove them from flowing biological fluids without any wash steps. To accomplish this, a microfabricated high-gradient magnetic field concentrator (HGMC) was integrated at one side of a microfluidic channel with two inlets and outlets. When magnetic micro- or nano-particles were introduced into one flow path, they remained limited to that flow stream. In contrast, when the HGMC was magnetized, the magnetic beads were efficiently pulled from the initial flow path into the collection stream, thereby cleansing the original fluid. Using this microdevice, living E. coli bacteria bound to magnetic nanoparticles were efficiently removed from flowing solutions containing densities of red blood cells similar to that found in blood. Because this microdevice allows large numbers of beads and cells to be sorted simultaneously, has no capacity limit, and does not lose separation efficiency as particles are removed, it may be especially useful for separations from blood or other clinical samples. This on-chip HGMC-microfluidic separator technology may potentially allow cell separations to be carried out in the field outside of hospitals and clinical laboratories.

Time-Controlled Microfluidic Seeding in nL-Volume Droplets To Separate Nucleation and Growth Stages of Protein Crystallization.
Gerdts CJ, Tereshko V, Yadav MK, Dementieva I, Collart F, Joachimiak A, Stevens RC, Kuhn P, Kossiakoff A, Ismagilov RF.
Angew Chem Int Ed Engl. 2006 Nov 13; [Epub ahead of print].
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No abstract available

A Versatile Approach for the Preparation of Thermosensitive PNIPAM Core-Shell Microgels with Nanoparticle Cores.
Karg M, Pastoriza-Santos I, Liz-Marzan LM, Hellweg T.
Chemphyschem. 2006 Nov 13;7(11):2298-2301.
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No abstract available

A Review of Poloxamer 407 Pharmaceutical and Pharmacological Characteristics.
Dumortier G, Grossiord JL, Agnely F, Chaumeil JC.
Pharm Res. 2006 Nov 11; [Epub ahead of print].
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Poloxamer 407 copolymer (ethylene oxide and propylene oxide blocks) shows thermoreversible properties, which is of the utmost interest in optimising drug formulation (fluid state at room temperature facilitating administration and gel state above sol-gel transition temperature at body temperature promoting prolonged release of pharmacological agents). Pharmaceutical evaluation consists in determining the rheological behaviour (flow curve or oscillatory studies), sol-gel transition temperature, in vitro drug release using either synthetic or physiological membrane and (bio)adhesion characteristics. Poloxamer 407 formulations led to enhanced solubilisation of poorly water-soluble drugs and prolonged release profile for many galenic applications (e.g., oral, rectal, topical, ophthalmic, nasal and injectable preparations) but did not clearly show any relevant advantages when used alone. Combination with other excipients like Poloxamer 188 or mucoadhesive polymers promotes Poloxamer 407 action by optimising sol-gel transition temperature or increasing bioadhesive properties. Inclusion of liposomes or micro(nano)particles in Poloxamer 407 formulations offers interesting prospects, as well. Besides these promising data, Poloxamer 407 has been held responsible for lipidic profile alteration and possible renal toxicity, which compromises its development for parenteral applications. In addition, new findings have demonstrated immuno-modulation and cytotoxicity-promoting properties of Poloxamer 407 revealing significant pharmacological interest and, hence, human trials are in progress to specify these potential applications.

External force-assisted cell positioning inside microfluidic devices.
Rhee SW, Taylor AM, Cribbs DH, Cotman CW, Jeon NL.
Biomed Microdevices. 2006 Nov 8; [Epub ahead of print].
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This paper describes straightforward approaches to positioning cells within microfluidic devices that can be implemented without special equipment or fabrication steps. External forces can effectively transport and position cells in preferred locations inside microfluidic channels. Except for centrifugal force-based positioning that can be used with any microfluidic channels, hydrodynamic and gravitational force-based positioning yield reproducible and biocompatible results when implemented with a microfluidic "module" that contains a barrier with embedded microgrooves. Primary rat cortical neurons, metastatic human breast cancer cells MDA-MB-231, NIH 3T3 mouse fibroblasts, and human umbilical vein endothelial cells (HUVECs) were compatible with the positioning processes. After positioning, cells attached, proliferated and migrated like control cells that were cultured on tissue culture dishes or glass coverslips. No apparent morphological differences were observed in positioned cells compared with control cells. Finally, to demonstrate a practical application of the methods, cells were placed in a single row along a wall inside a microfluidic chemotaxis chamber (MCC), and were exposed to stable concentration gradient of chemoattractant. Cell positioning allows that all cells get exposed to the same level of chemoattractant at the start of the experiment helping standardize cellular response.

Hormone-PAMAM Dendrimer Conjugates: Polymer Dynamics and Tether Structure Affect Ligand Access to Receptors.
Kim SH, Katzenellenbogen JA.
Angew Chem Int Ed Engl. 2006 Nov 6;45(43):7243-7248.
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No abstract available

Massively Parallel Dip-Pen Nanolithography with 55 000-Pen Two-Dimensional Arrays.
Salaita K, Wang Y, Fragala J, Vega RA, Liu C, Mirkin CA.
Angew Chem Int Ed Engl. 2006 Nov 6;45(43):7220-7223.
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No abstract available

Quantitative multispectral biosensing and 1D imaging using quasi-3D plasmonic crystals.
Stewart ME, Mack NH, Malyarchuk V, Soares JA, Lee TW, Gray SK, Nuzzo RG, Rogers JA.
Proc Natl Acad Sci SA. 2006 Nov 3; [Epub ahead of print].
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We developed a class of quasi-3D plasmonic crystal that consists of multilayered, regular arrays of subwavelength metal nanostructures. The complex, highly sensitive structure of the optical transmission spectra of these crystals makes them especially well suited for sensing applications. Coupled with quantitative electrodynamics modeling of their optical response, they enable full multiwavelength spectroscopic detection of molecular binding events with sensitivities that correspond to small fractions of a monolayer. The high degree of spatial uniformity of the crystals, formed by a soft nanoimprint te