Indocyanine green-encapsulated erlotinib modified chitosan nanoparticles for targeted chemo-photodynamic therapy of lung cancer cells

The outcome of application of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small-cell lung cancer (NSCLC) always suffers from acquired drug resistance. Its combination with other therapies has been explored with promising synergistic results. Photodynamic therapy (PDT) is an established treatment modality for NSCLC, but the low tumor selectivity of currently available photosensitizers (PSs) hampered the wide clinical application of PDT. Here, we synthesized erlotinib modified chitosan (ECs) by click coupling and developed ECs/indocyanine green (ICG) self-assembled nanoparticles (GECs) for combined targeted chemo-photodynamic therapy. GECs showed oval-shaped particles with a diameter of 267.5 nm, a zeta potential of -15.2 mV, and considerable photostability. In vitro release experiment showed that erlotinib and ICG could be slowly released from GECs in acidic condition with lysozyme. GECs were capable of generating reactive oxygen species (ROS) for PDT under near-infrared laser irradiation. GECs showed synergistic molecular targeted and photodynamic therapeutic effects in inhibition of cellular growth and induction of apoptosis in NSCLC cells. This study demonstrated that the GECs could be a promising platform by combination of targeted chemo-photodynamic therapy for NSCLC treatment.