Self-Assembly of Erlotinib-Platinum(II) Complexes for Epidermal Growth Factor Receptor-Targeted Photodynamic Therapy.

Due to cell mutation and self-adaptation, the application of clinical drugs with early epidermal growth factor receptor (EGFR)-targeted inhibitors is severely limited. To overcome this limitation, herein, the synthesis and in-depth biological evaluation of an erlotinib-platinum(II) complex as an EGFR-targeted anticancer agent is reported. The metal complex is able to self-assemble inside an aqueous solution and readily form nanostructures with strong photophysical properties. While being poorly toxic toward healthy cells and upon treatment in the dark, the compound was able to induce a cytotoxic effect in the very low micromolar range upon irradiation against EGFR overexpressing (drug resistant) human lung cancer cells as well as multicellular tumor spheroids. Mechanistic insights revealed that the compound was able to selectively degrade the EGFR using the lysosomal degradation pathway upon generation of singlet oxygen at the EGFR. We are confident that this work will open new avenues for the treatment of EGFR-overexpressing tumors.