(413h) Activatable Nanoparticles and Hydrogels: Integration of Synthetic Polymers, Polypeptides, and Oligonucleotides for the Detection and Treatment of Cancer

Polymeric nanoparticles and hydrogels that integrate a mechanism of user- or disease-controlled activation can be utilized in the development of contrast or therapeutic agents that provide increased selectivity for the targeted diseased tissues. Our group developed conductive polymer nanoparticles that absorb light in the near infrared range and which have capabilities for photothermal conversion. These particles are being investigated as agents for localized, laser-induced photothermal ablation of cancer cells as well as for combined phototherapy and chemotherapy. Similarly, we have developed of enzymatically activatable near infrared fluorescent polymeric nanoparticles as highly specific contrast agents for optical imaging and chemotherapeutic treatment of cancer. These particles provide an off-to-on fluorescence switch that is triggered by the cleavage of polypeptides that are anchored on the surface of the nanoparticles by proteolytic enzymes that are overexpressed in tumor tissue. More recently our group has been working on the development of DNA-enabled hydrogels that can have a wide range of functionality due to the ability of DNA to act as a biodegradable polymer, while also providing specificity for complementary strands and molecular targets. We have demonstrated DNA-crosslinked poly(ethylene glycol) hydrogels that can be degraded upon interaction with disease-related nucleases and their potential as controlled release systems. We are currently working to develop similar hydrogels that can degrade upon interaction to molecular targets through the inclusion of hybridized aptamer/DNA complexes as crosslinkers. This talk will describe the synthesis, characterization, and in vitro evaluation of the nanoparticle and hydrogel systems described above, and provide a glance into the enormous potential of responsive polymeric biomaterials in biomedicine.