Background
Non-small cell lung cancer (NSCLC) is a worldwide health threat with high annual morbidity and mortality. Chemotherapeutic drugs such as paclitaxel (PTX) have been widely applied clinically. However, systemic toxicity due to the non-specific circulation of PTX often leads to multi-organ damage, including to the liver and kidney. Thus, it is necessary to develop a novel strategy to enhance the targeted antitumor effects of PTX.
Conclusions
Our study provides a nanovesicle-based delivery platform to promote the efficacy of chemotherapeutic drugs with fewer side effects. This novel strategy may ameliorate the present obstacles to the clinical treatment of lung cancer.
Methods
Here, we engineered exosomes derived from T cells expressing the chimeric antigen receptor (CAR-Exos), which targeted mesothelin (MSLN)-expressing Lewis lung cancer (MSLN-LLC) through the anti-MSLN single-chain variable fragment (scFv) of CAR-Exos. PTX was encapsulated into CAR-Exos (PTX@CAR-Exos) and administered via inhalation to an orthotopic lung cancer mouse model.
Results
Inhaled PTX@CAR-Exos accumulated within the tumor area, reduced tumor size, and prolonged survival with little toxicity. In addition, PTX@CAR-Exos reprogrammed the tumor microenvironment and reversed the immunosuppression, which was attributed to infiltrating CD8+ T cells and elevated IFN-γ and TNF-α levels. Conclusions: Our study provides a nanovesicle-based delivery platform to promote the efficacy of chemotherapeutic drugs with fewer side effects. This novel strategy may ameliorate the present obstacles to the clinical treatment of lung cancer.