DEVELOPMENT OF FUNCTIONAL NANOCERIA FOR TARGETED IMAGING AND TREATMENT OF NON-SMALL-CELL LUNG CANCER
Significant progression of lung cancer towards death is a major concern in today’s world. Among all other lung cancers, K-RAS driven Non-Small-Cell Lung Cancer (NSCLC) represents major cause of death amongst smokers. However, absence of specificity, multi drug resistance (MDR) and severe side effects often impose serious limitations to the existing therapies. Therefore, development of new and more effective therapies remains essential and challenging. Recently, nanotechnology has introduced novel avenues for the diagnosis and personalized treatment options for cancer. Among many nanomaterials, cerium oxide nanoparticles (nanoceria, NC) are considered as excellent material due to their unique redox property and showed exceptional antitumor activity when incubated with cancer cells. Herein, we report a novel targeted NC platform loaded with unique ‘combination therapy’ using two therapeutic drugs: 1) doxorubicin (Doxo) and 2) Hsp90 inhibitor ganetespib (GT), for the timely diagnosis and effective treatment of NSCLC. Doxorubicin is a well-known anthracycline chemotherapeutic drug and ganetespib, a potent inhibitor of HSp90 which is developed to treat the multiple solid tumor and hematologic cancers. This research work includes the synthesis of novel polyacrylic acid-coated functional nanoceria (PNC) for the diagnosis and targeted treatment of lung cancers. Our tiny nanoceria (D = 57±2 nm) plays an important role for the successful cargos encapsulation through solvent diffusion method and internalization specifically to cancer cells. Using “Click” chemistry, the surface carboxylic acid groups of NC was decorated with folic acid to target folate-receptor over-expressing lung cancer cells (A549 cells, NSCLC). The formulated drugs-encapsulating NC shows more than 80% lung carcinoma cell death within 48 h of incubation. Further in vitro studies including cytotoxicity studies, drug release profiles, and fluorescence microscopic studies, ROS and apoptosis assays indicated for the tremendous therapeutic application of our redox NC platform for cancer treatment.