A redox-responsive cationic liposome for PTX lung-specific delivery and pulmonary carcinoma therapy

Successful chemotherapy of pulmonary carcinoma requires both efficient lung accumulation and controlled intracellular drug release. Here, we developed a lung-tropic redox-responsive paclitaxel liposome (Lu-rePTX/Lipo) by co-assembling the cationic lipid DOTAP, a disulfide-linked phospholipid–paclitaxel conjugate (GPCssPTX), and DSPE-PEG2000. The optimized formulation showed a particle size below 200 nm, favorable lung accumulation, and glutathione-triggered PTX release. Increased DOTAP incorporation enhanced lung tropism and promoted PTX accumulation in lung tissue. Lu-rePTX/Lipo also exhibited enhanced cellular uptake and stronger cytotoxicity against LLC1 cells, while maintaining reduced toxicity toward normal cells due to redox-selective drug release. In an LLC1-bearing mouse model, Lu-rePTX/Lipo achieved superior antitumor efficacy compared with control formulations. These results demonstrate that integrating DOTAP-mediated lung tropism with a redox-responsive phospholipid prodrug strategy provides a promising platform for pulmonary carcinoma therapy.