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