posted on 2024-01-06, 15:04authored byHaobing Wang, Yidan Lai, Dan Li, Johannes Karges, Pingyu Zhang, Huaiyi Huang
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.