Since 2004, Alliance researchers have focused on developing new nanomaterials for use in diagnosing and treating cancer and assessing their behavior in the body. With a substantial knowledge base to inform their efforts, Alliance investigators have created targeted, nano-enabled agents with the aim of moving these new constructs into human clinical trials. These efforts have been aided by formal interactions between the National Cancer Institute (NCI), the U.S. Food and Drug Administration (FDA), and the National Institute of Standards and Technology (NIST) to establish standards for regulating clinical trials of nanotechnology-enabled products.
Alliance researchers are making promising advances in bringing nanotechnology-enabled treatments and diagnostics closer to the clinic. Information on clinical trials involving nanotechnology can be found in Nanotechnology in Clinical Trials section. Visit News and Highlights to read recent news coverage of cancer nanotechnology accomplishments.
- Drs. Cheryl Williams and Jeff Brinker — co-principal investigators of the University of New Mexico (UNM) Cancer Nanotechnology Platform Partnership have produced an effective strategy that uses nanoparticles to treat tumors with a mélange of anticancer agents. This strategy relies on using silica nanoparticles honeycombed with cavities that can store large amounts and varieties of drugs loaded inside a lipid-based nanoparticle known as a liposome. The UNM researchers have also developed a parallel nano-platform using virus-like particles (VLPs) of bacteriophage MS2. These VLPs are protein capsids that are highly uniform in size and shape and capable of encapsulating large amounts of cargo in their interior.
- Dr. Julia Ljubimova's group has detected a subtle shift occurring in the molecular makeup of the most aggressive type of brain tumors, glioblastoma multiforme. With further study, the group found that a specific protein called laminin-411 plays a major role in a tumor's ability to build new blood vessels to support its growth and spread. By employing nanparticles as a drug delivery agent, the research team has created a "nanobioconjugate" drug that may be given by intravenous injection and carried in the blood to target the brain tumor. The new nanobioconjugate comprises several key components, each with a role in getting a powerful antitumor agent into brain tumors. The nanoparticle that makes up the bulk of this construct is made of a biodegradable polymer known as polymalic acid that is produced by slime molds and that will self-assemble into nanoparticles. The researchers attached a variety of molecules to the polymer backbone. Each of these molecules has its own role to play in getting this construct to brain tumors and killing them. One set of molecules enables the resulting nanoparticle to cross the blood-brain barrier, while another helps the nanoparticle enter the cell. A third set of molecules cause tiny compartments inside cells, known as endosomes, to rupture, releasing the nanoparticle into the cell's cytoplasm. Finally, two different antisense oligonucleotides – the actual anticancer agents – block the production of laminin-411. These antisense agents are not toxic to non-malignant cells.
- Researchers at the University of North Carolina (UNC) CCNE led by Dr. Otto Zhou have successfully designed and manufactured a prototype stationary digital breast Tomosynthesis scanner by combining the strength of their unique carbon nanotube based x-ray source array technology with Hologic's advanced detection system. The UNC prototype is aimed at improving early detection of breast tumors by overcoming limitations of current digital tomosynthesis scanners, such as long scanning time, patient and x-ray source motion blurring, and low sensitivity for micro-calcification.
- Shan Wang's team from the Center for Cancer Nanotechnology Excellence and Translation at Stanford University has developed a new biosensor microchip that could significantly speed up the process of drug development. The microchips, packed with highly sensitive magnetic nanosensors, analyze how proteins bind to one another, a critical step for evaluating the effectiveness and possible side effects of a potential medication. A single centimeter-sized array of the nanosensors can simultaneously and continuously monitor thousands of times more protein-binding events than any existing sensor. The new sensor is also able to detect interactions with greater sensitivity and deliver the results significantly faster than the present "gold standard" method.
- Ralph Weissleder's group from the MIT-Harvard CCNE has developed a fast, portable, and potentially inexpensive method of detecting cancer from human biopsy samples by using a handheld molecular imaging device in combination with magnetic nanoparticles and a smartphone. Initial results obtained using fine need biopsies taken from human cancer patients show this device trumps traditional pathological methods, both in terms of speed (less than one hour) and diagnostic accuracy (96 percent) compared to three days for traditional histopathology.
- Drs. Mansoor Amiji and Zhen-feng Duan and their team from Northeastern University crafted nanoparticles from a biodegradable polymer blend that first releases a powerful anticancer drug and then delivers an agent that tricks a drug-resistant cell into committing suicide. Now, tests in mice with human breast cancer have shown that these blended nanoparticles – designed to fight drug-resistant cancers – are effective in maintaining high levels of both drugs in the vicinity of tumors.
- Dr. Michael Cima's team at the MIT-Harvard CCNE has developed an implantable device that was capable of monitoring the level of a cancer biomarker for a month using a conventional MRI scanner. Such measurements could provide early clues of metastasis and evidence that a drug is having the desired effect on a tumor.
- Nanotechnology researchers have known for years that RNA is a promising tool for nanotherapy, but the difficulties of producing long-lasting, therapeutic RNA that remains stable and non-toxic while entering targeted cells have posed challenges for their progress. Now, a team of investigators led by Peixuan Guo, co-principal investigator of the University of Cincinnati Cancer Nanotechnology Platform Partnership, found a method for producing RNA nanoparticles and testing their safety in the delivery of therapeutics to targeted cells.
- Dr. Joseph DeSimone, from the University of North Carolina (UNC) CCNE, has developed a manufacturing technique capable of mass production of quality particles with fully controllable and reproducible size, shape, matrix composition and flexibility and surface chemistry. This PRINT (Particle Replication In Non-wetting Templates) technology is a soft lithographic imprint technique to produce particles from diverse biologically and pharmaceutically relevant precursors.
The Alliance has also made important advances in its multidisciplinary collaboration efforts. Recent accomplishments include:
Nanotechnology Characterization Laboratory (NCL)
The National Cancer Institute's Nanotechnology Characterization Laboratory (NCL), part of NCI's Alliance for Nanotechnology in Cancer, was established in 2004 to accelerate the translation of promising nanotechnology-derived cancer treatments into clinical applications. The NCL is a formal interagency collaboration between NCI, NIST, and FDA and is operated through the NCI's Federally Funded Research & Development Center (FFRDC) at SAIC/NCI-Frederick.
- The NCL has developed a three-tiered Assay Cascade of tests, including physicochemical characterization, in vitro assessment and in vivo evaluation for safety and efficacy, as a standard tool for the preclinical characterization of biomedical nanomaterials. Over 200 different nanoparticle formulations have been evaluated by the NCL. Nearly 90% of these formulations came from academia, industry, and government.
- NCL, in collaboration with NIST and the American Society for Testing and Materials (ASTM), hosted a workshop on Answering the Need for Standardization in Nanomaterial Measurements. This workshop marked the conclusion of an ASTM-sponsored, NCL and NIST-coordinated inter-laboratory study (ILS) involving more than 60 participating laboratories. This study helped elucidate sources of data variability in nanoparticle characterization.
- NCL initiated a study of the stability of various nanoparticles under conditions mimicking those used to sterilize medical devices in collaboration with the FDA's Center for Devices and Radiological Health (CDRH).
- NCL staff continued to contribute directly to the education of the next generation of nanotechnologists through the Foundation for the Advanced Education in the Sciences (FAES) Bio-Trac biotechnology training courses in nanomedicine. NCL established an NCL-NIST postdoctoral training program in chemistry and external organizations such as the Institute for Food Technologists (IFT) continue to leverage NCL expertise and publications in their educational efforts.
Data sharing through caNanoLab
In collaboration with the NCI Center for Biomedical Informatics and Information Technology (CBIIT), the NCI has established the cancer Nanotechnology Characterization Portal (caNanoLab), which is a database to house the results from NCL's and the Alliance investigators' studies and make them accessible to the research community. caNanoLab provides access to information on nanomaterials composition, physico-chemical characterizations, in vitro characterization (cytotoxicity, blood contact properties, immune cell functions), nanomaterials pharmacokinetics and toxicity, protocols supporting nanotechnology characterizations, nanomaterials synthesis and preparation, radiolabeling and safety and publications and reports from nanotechnology studies in cancer research.
caNanoLab is working with the nanotechnology biomedical community to develop standards for capturing information on nanomaterials and their characterization in a structured fashion, in support of cross-particle analysis and advanced visualization of structure-activity relationships. These standards will assist in engineering nanomaterials for optimal biodistribution and identifying the impact of particle physicochemical structure on biological activity.
The Alliance has over 250 disclosures or patents filed to date and strong relationships with many biotechnology companies. In addition, the Alliance has played a vital role in attracting a number of high-quality research proposals to be funded through the Small Business Innovation Research (SBIR) program on topics that support the mission of the Alliance. The basis for the program is to provide early-stage technology financing in order to promote innovation for developing and commercializing novel technologies and products to prevent, diagnose, and treat cancer. Companies spun out of Alliance laboratories include:
- Calando Pharmaceuticals is developing the nanocarrier technology Cyclosert™, developed through the work at the Nanosystems Biology Cancer Center. This technology is used to conduct two cancer clinical trials. Please visit Nanotechnology in Clinical Trials in this website.
- BIND Biosciences, which has received SBIR funding, is developing targeted therapeutic nanoparticles developed at the MIT-Harvard Center of Cancer Nanotechnology Excellence.
- Liquidia Technologies, another SBIR awardee, was spun out of the Carolina Center of Cancer Nanotechnology Excellence to commercialize a novel design and manufacturing platform for nanoparticles.
- Xintek, another Carolina Center of Cancer Nanotechnology Excellence spinout and SBIR awardee, uses thin film technologies to develop carbon nanotubes to aid in medical imaging.
- MagArray, an SBIR awardee, is commercializing a technology developed at the Center for Cancer Nanotechnology Excellence Focused on Therapy Response that uses engineered magnetic silicon nanoparticles to detect trace levels of tumor antigens in blood.
- PDS Biotechnology received SBIR funding to commercialize the Versamune™ nanoparticle drug delivery technology that was developed at the Carolina Center of Cancer Nanotechnology Excellence.