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

Nanomedicine delivery systems combined with photodynamic therapy, improve targeted cancer enrich-ment, 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 struc-ture ruptures, directly consuming GSH and further inactivating GPX4, thereby establishing a specific anti-cancer 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 microenviron-ment with high GSH level and acidic environment, this dual-responsive strategy combines a photody-namic and ferroptotic effect; it might improve the treatment efficacy of head and neck cancers.

Automated summary

This study aimed to develop a drug carrier, ZIF-8@ssPDA, for head and neck cancer treatment. The ZIF-8 structure efficiently loaded the photosensitizer Ce6, while the ssPDA structure could rupture in response to the tumor microenvironment, consuming glutathione and inactivating GPX4 to exert an anti-cancer effect through ferroptosis. Furthermore, the Ce6@ZIF-8 structure could release Ce6 in the acidic tumor microenvironment, generating singlet oxygen under near-infrared laser excitation for photodynamic therapy.