Dual-responsive nanosystem for precise molecular subtyping and resistant reversal of EGFR targeted therapy

Abstract

The clinical outcome of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors is limited by the ambiguous molecular subtypes of non-small cell lung cancer (NSCLC) patients and the emergence of drug-resistance. Here, a nanotheranostic agent ECMI, which is indocyanine green (ICG)-loaded mesoporous silica nanoparticles lidded with ZnO QDs and wrapped with erlotinib-modified chitosan, was developed for accurately determination of molecular subtypes and synergistic therapy. The erlotinib could guide ECMI into EGFR-mutated NSCLC cells and acquire a pH/redox dual-responsive release of ICG for precise fluorescent imaging. The ECMI could exert synergistic photodynamic/molecular targeted therapeutic effects under near-infrared irradiation in either erlotinib-sensitive or erlotinib-resistant EGFR-mutated NSCLC cells. In vivo experiments further showed that ECMI had distinct distribution behaviors in different NSCLC models and demonstrated synergistic anticancer effects. These results indicated that ECMI could be a promising nanotheranostic agent to treat EGFR-mutated NSCLC, and could provide a new perspective for individualized treatment.