Co-delivery of Doxorubicin and Afatinib with pH-responsive Polymeric Nanovesicle for Enhanced Lung Cancer Therapy

Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death. Nanoparticle-mediated multidrug combination treatment has been proven to be a feasible strategy to overcome these challenges. In the present study, amphipathic block polymer of methoxyl poly(ethylene glycol)-poly(aspartyl(dibutylethylenediamine)-co-phenylalanine)(m PEG-P(Asp(DBA)-co-Phe)) was synthesized and self-assembled into p H-responsive polymeric vesicle. The vesicle was utilized to co-deliver cancer-associated epidermal growth factor(EGFR) inhibitor of afatinib and DNA-damaging chemotherapeutic doxorubicin hydrochloride(DOX) for enhanced non-small-cell lung cancer(NSCLC) therapy. As evaluated in vitro, the p H-responsive design of nanovesicle resulted in a rapid release of encapsulated drugs into tumor cells and caused enhanced cell apoptosis. In addition, in vivo therapeutic studies were conducted and the results evidenced that the co-delevery of DOX and afatinib using p H-sensitive nanovector was a promising strategy for NSCLC treatment.