KSEF RDE: Targeted Peptide-Conjugated Nanoparticles for the Enhancement of Radiation via Hyperthermia for Lung Cancer Applications

Non-small cell lung cancer is the leading cause of cancer-related deaths in the United States and is also very prevalent in the state of Kentucky. Although surgery, chemotherapy and radiation are the current conventional treatments, recent work has shown that combining treatments such as radiation with hyperthermia is more effective in treating lung cancer. The purpose of this study is to develop and characterize peptide-conjugated dextran-coated iron oxide magnetic nanoparticles for enhanced tumor targeting and penetration, allowing for improved treatment of lung cancer via enhancement of radiation therapy by magnetically-mediated hyperthermia. Magnetically-mediated hyperthermia, the heating of tissue using heat generated by nanoparticles in the presence of an alternating magnetic field, shows great promise in overcoming the limitations of current hyperthermia treatments due to the potential to deliver heat directly to the tumor site. However, passive targeting of nanoparticles to tumor sites is not enough to accumulate a sufficient concentration of particles at the tumor site in order to induce effective hyperthermia. Active targeting with ligands can improve the concentration of nanoparticles at the tumor site, but they often lack the ability to penetrate into the tumor and therefore, agglomerate on the tumor surface. In this study, nanoparticles will be conjugated with a tumor homing peptide, CREKA, and a tumor penetrating peptide, iRGD (internalizing RGD), to promote penetration into tumor. iRGD is a newly developed tumor-penetrating peptide that has been shown to attach to the tumor surface and penetrate throughout the tumor while attached to a drug or nanoparticle. CREKA recognizes fibrin-associated plasma proteins, which are present in cancerous tumors and tumor vasculature but not in normal, healthy tissue. Particles will be developed and characterized and their ability to penetrate tumors will be evaluated using 3D tumor spheroid models.