Novel Chemoradiotherapeutic Magnetic Nanoparticles for Targeted Treatment of Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer-related death in the United States and 85% of all lung cancers are classified as non-small cell (NSCLC). Unfortunately, NSCLC is extremely difficult to treat and the survival rates are low; in 2012, the five year survival rate was only 17%. An innovative approach that may ultimately allow for the clinician to target and aggressively reduce tumor burden in patients with NSCLC will be presented. Platinum (Pt)-based radiosensitizers; cisplatin, carboplatin, oxaliplatin and holmium-166 radionuclide (166Ho; E_β-max = 1.84 MeV; t½= 26.8 h) have been incorporated in a garnet magnetic nanoparticle (Pt-HoIG) for selective delivery to tumors using an external magnet. The Pt anticancer drugs can be used as radiosensitizers, and the ¹⁶⁶Ho emits beta particles and gamma photons, which can be used for therapy and imaging, respectively. A major obstacle in therapy is the non-specificity of current treatments. Nonspecific anticancer drugs administered via intravenous injection are distributed throughout the entire body and are harmful to healthy tissues as well as tumor sites, leading to significant side effects. The nanoparticles reported here could potentially deliver their chemoradiotherapeutic ‘cargo’ directly to tumors in a patient, guided by a magnet. The HoIG and Pt-HoIG nanoparticles were characterized using PXRD, SEM, EDX, TEM, ICP-MS, and Zeta potential measurements. Neutron activated cisplatin-HoIG and oxaliplatin-HoIG showed greater toxicity than HoIG, free cisplatin and oxaliplatin toward NSCLC A549 cells. Thus, cisplatin and oxaliplatin act synergistically with the radioactive Ho making nontoxic doses of radiation extremely effective.