Targeting CD36 is a new therapeutic approach in cancer therapy. CD36 is a member of the class B scavenger receptor family of cell surface proteins that facilitates the uptake of free fatty acids for lipid metabolism. CD36 promotes tumour growth by fueling cancer metastasis, supporting drug resistance, and modulating tumor immunity. Recent studies indicate that CD36 is upregulated in ovarian tumors. We hereby engineered photoactivatable Pt(IV) prodrugs that harness CD36 to target ovarian cancer cells. The Pt(IV) compounds mimic the fatty acid structure and act as “Trojan horse” to exploit CD36 to facilitate their cell entry. CD36-dependent cell entry of the Pt(IV) complexes was validated by graphite furnace atomic absorption spectroscopy using ovarian cancer cells with different expression levels of CD36 and a CD36 inhibitor, SSO. Upon entering cancer cells, these Pt(IV) metallodrugs can be activated upon light irradiation (490–805 nm). Photoactivation of the Pt(IV) compounds is driven by photoinduced electron transfer from the attached fluorophore to the metal center. Light irradiation enhances cytotoxicity of the Pt(IV) metallodrugs up to 20 times against ovarian cancer cells and facilitates elimination of ovarian cancer stem cells.

Photoactivatable platinum(IV) prodrugs harnessing CD36 for ovarian cancer therapy

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.