Chitosan coated ZnO/Tio2/Gd2O3 nano composites for improved rapamycin delivery in non-small cell lung cancer.

The increasing prevalence of Non-Small Cell Lung Cancer (NSCLC) demands innovative therapeutic strategies. Rapamycin, an mTORC1 inhibitor, shows promise in cancer therapy but is limited by drug resistance and low bioavailability. This study develops a novel rapamycin-loaded chitosan-coated ZnO/Tio2/Gd2O3 nano-composite (RNC) incorporating ZnO, TiO₂, and Gd₂O₃ nanoparticles, coated with chitosan, to enhance rapamycin delivery and efficacy against A549 cancer cells. The RNC demonstrated a drug loading efficiency of 100 % and a controlled release profile, achieving complete release over 6 h. Cytotoxicity assays revealed an LC₅₀ of 31 μg mL-1 for A549 cells and 103 μg mL-1 for L929 normal cells, indicating selective toxicity. The RNC significantly elevated ROS levels (fluorescence intensity: 10,281.70 AU) and induced G0/G1 cell cycle arrest in 80.5 % of A549 cells. Increased expression of caspase-3 and p62 confirmed enhanced apoptosis and autophagy. These results demonstrate that the RNC formulation effectively overcomes the limitations of rapamycin, offering a promising approach for targeted NSCLC therapy.