Co-delivery of erlotinib and doxorubicin by MoS2 nanosheets for synergetic photothermal chemotherapy of cancer

Abstract Time-staggered administration of erlotinib (Er) and doxorubicin (DOX) provides significantly enhanced apoptosis of lung cancer cells, but this administration approach has not been translated successfully to the clinic due to discrepant formulation parameters and different routes of administration. Here, we developed a MoS2-based multifunctional nanoplatform capable of achieving co-delivery of Er and DOX and controlled drug release for effective cancer therapy. Er was first connected to MoS2 nanosheets via click chemistry with polyethylene glycol (PEG) as a linker, followed by incorporation of DOX. The resulting MoS2-PEG-Er/DOX converted absorbed near-infrared (NIR) light into heat, which achieved the controlled release of DOX and induced the photothermal ablation of cancer cells. After cellular uptake of MoS2-PEG-Er/DOX, the loaded Er directly inhibited epidermal growth factor receptor (EGFR) signaling cascade to suppress cancer cell proliferation and promote the dynamic rewiring of apoptotic pathway, which sensitized cancer cells to the action of the NIR-triggered released DOX. More importantly, MoS2-PEG-Er/DOX upon NIR irradiation achieved the synergetic photothermal chemotherapy of cancer, which effectively inhibited tumor growth in lung cancer cell-bearing mice. The results of this study demonstrate the excellent antitumor effect of MoS2-PEG-Er/DOX, providing a promising strategy for clinical treatment of cancer.