Chemoradiotherapeutic Magnetic Nanoparticles for Targeted Treatment of Nonsmall Cell Lung Cancer

Lung cancer is the leading cause of cancer-related death in the United States and approximately 85% of all lung cancers are classified as nonsmall cell (NSCLC). We here use an innovative approach that may ultimately allow for the clinician to target tumors and aggressively reduce tumor burden in patients with NSCLC. In this study, a platinum (Pt)-based chemotherapeutic (cisplatin, carboplatin, or oxaliplatin) and holmium-165 (Ho), which can be neutron-activated to produce the holmium-166 radionuclide, have been incorporated together in a garnet magnetic nanoparticle (HoIG-Pt) for selective delivery to tumors using an external magnet. The synthesized magnetic HoIG nanoparticles were characterized using PXRD, TEM, ICP-MS, and neutron-activation. Platinum(II) drugs were incorporated onto HoIG, and these were characterized using FTIR, EDX, ICP-MS, and zeta potential measurements, and in vitro and in vivo studies were performed using a HoIG-platinum system. Results indicate that neutron-activated (166)HoIG-cisplatin is more toxic toward NSCLC A549 cells than is blank (166)HoIG and free cisplatin, and that when an external magnetic field is applied in vivo, higher tumor to liver ratios of Ho are observed than when no magnet is applied, suggesting that magnetic targeting is achieved using this system. Furthermore, an efficacy study demonstrated the inhibition of tumor growth by chemoradiotherapeutic magnetic nanoparticles, compared to no treatment controls.