(449c) Development of Peptide-Conjugated Iron Oxide Nanoparticles for Hyperthermia Treatment of Cancer

Hyperthermia, the heating of tissue between 42 and 45°C, has been shown to enhance the effects of radiation and chemotherapeutics, but current methods of hyperthermia often result in severe side effects due to lack of localization and overheating of tissue. Magnetically mediated hyperthermia provides the opportunity for localized heating, however, this method is currently limited by the lack of particle penetration into tumor tissue. In this research, a nanoparticle system composed of an iron oxide core with a crosslinked dextran coating functionalized with the tumor homing peptide, CREKA, has been developed to overcome this limitation by homing to and penetrating into tumor tissue. The iron oxide core allows for particle heating upon exposure to an alternating magnetic field while the dextran coating stabilizes the particles in suspension and decreases the cytotoxicity. The overall goal of this study was to optimize CREKA-conjugated iron oxide nanoparticles for enhanced tumor homing and penetration for effective hyperthermia treatment applications. This specific particle system can enhance particle accumulation at the tumor site, providing a high enough concentration to induce hyperthermia conditions. The particles were characterized for size, stability, biocompatibility, and heating capabilities. The particles were stable in PBS and media over at least twelve hours, have a hydrated diameter of 50 nm, and can generate a significant amount of heat to raise solution temperatures well into the hyperthermia range. The cytotoxicity of the particles was analyzed through studies on A549 lung cancer cells for low particle concentrations with high exposure time and results determined that the particles have low cytotoxicity over both time frames and concentrations. Fibrinogen clots were used to determine the binding affinity of CREKA conjugated iron oxide nanoparticles compared to non-targeting nanoparticles. The binding and uptake of CREKA conjugated iron oxide nanoparticles into multicellular spheroids and monolayer cell cultures was also evaluated. This particle system is novel in that it incorporates the heating properties of iron oxide with the tumor homing properties of CREKA, to enhance particle homing to tumor sites.