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Chitosan coated ZnO/Tio2/Gd2O3 nano composites for improved rapamycin delivery in non-small cell lung cancer
Sanjeev K Ganesh1, Arghya Chakravorty2, Vimala Raghavan2
1School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Abstract:
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.
Insights
This study introduces a novel nano-composite drug delivery system for rapamycin, enhancing its effectiveness against Non-Small Cell Lung Cancer (NSCLC) by improving delivery and overcoming resistance.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Non-Small Cell Lung Cancer (NSCLC) prevalence necessitates advanced therapies.
- Rapamycin (mTORC1 inhibitor) shows therapeutic potential but faces limitations like drug resistance and poor bioavailability.
Purpose of the Study:
- To develop and evaluate a novel rapamycin-loaded chitosan-coated ZnO/TiO₂/Gd₂O₃ nano-composite (RNC).
- To enhance rapamycin delivery and efficacy against A549 cancer cells for targeted NSCLC therapy.
Main Methods:
- Fabrication of a chitosan-coated ZnO/TiO₂/Gd₂O₃ nano-composite loaded with rapamycin.
- Assessment of drug loading efficiency, controlled release profile, and cytotoxicity against A549 and L929 cells.
- Evaluation of reactive oxygen species (ROS) levels, cell cycle arrest, apoptosis (caspase-3), and autophagy (p62) induction.
Main Results:
- The RNC achieved 100% drug loading efficiency and controlled release over 6 hours.
- Selective toxicity was observed with an LC₅₀ of 31 μg/mL for A549 cells versus 103 μg/mL for L929 normal cells.
- RNC significantly increased ROS levels, induced G0/G1 cell cycle arrest in 80.5% of A549 cells, and enhanced apoptosis and autophagy.
Conclusions:
- The developed RNC formulation effectively overcomes rapamycin's limitations.
- This nano-composite offers a promising strategy for targeted Non-Small Cell Lung Cancer therapy.
