Carbonic anhydrase IX-targeted nanovesicles potentiated ferroptosis by reworking the intracellular setting for synergetic most cancers remedy


Ferroptosis is one important form of regulated cell demise for tumor suppression, but it nonetheless presents challenges of low effectivity because of the intracellular alkaline pH and aberrant redox standing. Herein, we reported a carbonic anhydrase IX (CA IX)-targeted nanovesicle (PAHC NV) to potentiate ferroptosis by reworking the intracellular setting. CA IX inhibitor 4-(2-aminoethyl) benzene sulfonamide (AEBS) was anchored onto nanovesicles loaded with hemoglobin (Hb) and chlorin e6 (Ce6). Upon reaching tumor areas, PAHC might be internalized by most cancers cells particularly via CA IX concentrating on and intervention. Afterwards, the binding of AEBS may elicit intracellular acidification and alter redox homeostasis to spice up the lipid peroxidation (LPO) stage, thus aggravating the ferroptosis course of. In the meantime, Hb served as an iron reservoir that might effectively evoke ferroptosis and launch O2 to ameliorate tumor hypoxia. With the assistance of self-supplied O2, Ce6 produced a plethora of 1O2 for enhanced photodynamic remedy, which in flip favored LPO accumulation to synergize ferroptosis. This examine presents a promising paradigm for designing nanomedicines to intensify ferroptosis-based synergetic therapeutics by means of reworking the intracellular setting.

Graphical abstract: Carbonic anhydrase IX-targeted nanovesicles potentiated ferroptosis by remodeling the intracellular environment for synergetic cancer therapy

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