(656c) Magnetic Hydrogel Nanocomposites for Synergistic Chemotherapy and Hyperthermia-Based Treatment of Cancer

Hyperthermia, the heating of tissue to 41 to 45°C, has been shown to improve the efficacy of cancer therapy when used in conjunction with irradiation and/or chemotherapy. This can be done through the utilization of biomaterials which can be delivered at tumor sites and remotely heated from outside the body while simultaneously controlling the delivery of therapeutic drugs. One such potential class of materials is magnetic hydrogel nanocomposites which are composed of biocompatible polymeric systems and magnetic nanoparticulates capable of heating upon exposure to an electromagnetic field. In this research, hydrogel nanocomposites have been developed that can be implanted or injected within a tumor to control the delivery of both heat and chemotherapeutic agents. The nanocomposites studied for this project include a stealth, poly(ethylene glycol) (PEG)-based system and a poly(β-amino ester) (PBAE)-based biodegradable system. Iron oxide nanoparticles were physically entrapped in these materials during polymerization to provide the remote heating mechanism of these systems. The capability of the hydrogels to be heated in an alternating magnetic field at various temperatures depending on the strength of the field was demonstrated. Swelling analysis was done and showed temperature-responsive behavior of PEG gels in their swollen state. These gels were determined to be non-toxic to murine fibroblasts indicating their potential biocompatibility. M059K glioblastoma cells were heated to thermoablative temperatures (above 55°C) via gels exposed to the AMF, and the resultant cell death was observed. PBAE degradable gels have been evaluated that will have the ability to heat via the iron oxide nanoparticles and have controlled release of chemotherapeutic drugs. The degradation profile of these gels can be tailored by the ratio of macromers used, and again, remote heating has been successfully demonstrated. In summary, these systems have the ability to be remotely heated and to deliver drugs to specific sites, which make them viable systems for treating deep-seated or reoccurring tumors.