Oligonucleotides Create Versatile Coating for Nanoscale Imaging Agents
Nanoparticles made of metals such as gold or iron oxide show tremendous promise as contrast agents for molecular imaging, but turning promise into clinical utility requires adding tumor targeting molecules to the surfaces of these nanoparticles. A new coating technique that uses oligonucleotides to tether targeting molecules securely to a nanoparticle’s surface could provide a versatile method for creating such targeted nanoparticles.
Reporting their work in the journal Bioconjugate Chemistry, Rebecca Richards-Kortum, Ph.D., and colleagues describe a method for using sulfur-containing derivatives of DNA that bind tightly to the surface of gold nanoparticles. The researchers then use a complementary DNA sequence to link the DNA-coated nanoparticle to a targeting ligand. The resulting oligonucleotide-linked nanoparticles are much smaller than similar imaging agents constructed by absorbing targeting proteins directly onto the surfaces of gold nanoparticles. The oligonucleotide tethers also produce a construct that is more stable under physiological conditions.
Using their new methodology, the investigators created imaging agents designed to detect the epidermal growth factor receptor (EGF) using either an EGF peptide or an antibody that binds to the receptor. The researchers also created a contrast agent designed to recognize the folate receptor that is overexpressed in many tumors, as well as a contrast agent that also contains a fluorescent marker that allows for multimodal imaging using both confocal reflectance imaging and standard fluoresence imaging. In each case, the contrast agents provided a significant signal boost that was detected easily using the appropriate imaging technique.
This work is detailed in the paper “Oligonucleotide-coated metallic nanoparticles as a flexible platform for molecular imaging agents.” This paper was published online in advance of print publication. An abstract of this paper is available through PubMed.View abstract