Photodynamic and ferroptotic Ce6@ZIF-8@ssPDA for head and neck cancer treatment

Abstract

Nanomedicine delivery systems combined with photodynamic therapy, improve targeted cancer enrichment, reduce side effects, and enhance anticancer efficacy. Additionally, ferroptosis has emerged as a novel cancer-killing mechanism, with great potential in cancer treatment. The study aimed to treat head and neck cancers by manufacturing ZIF-8@ssPDA as a drug carrier for the chlorin e6 (Ce6) photosensitizer in response to dual stimuli of the tumor microenvironment. The ZIF-8 structure can efficiently load Ce6, and polydopamine modified with a disulfide bond (ssPDA) is evenly and densely distributed on the ZIF-8 surface. In tumor microenvironments where glutathione (GSH) concentrations are high, the ssPDA structure ruptures, directly consuming GSH and further inactivating GPX4, thereby establishing a specific anticancer effect through the ferroptosis pathway. Furthermore, the Ce6@ZIF-8 structure responsively collapses in the acidic tumor microenvironment, releasing loaded Ce6. Under the excitation of a 660-nm near-infrared laser, large singlet oxygen can be generated from released Ce6 within a short period, exerting a strong photodynamic anticancer effect. Depending on the characteristic tumor microenvironment with high GSH level and acidic environment, this dual-responsive strategy combines a photodynamic and ferroptotic effect; it might improve the treatment efficacy of head and neck cancers.