• • TPE-SPyCx@BSA generates ·OH exclusively from water, confirmed by isotope tracing, with a VB potential that meets the thermodynamic threshold for water oxidation (≥ +2.38 V vs. NHE). This eliminates dependence on tumor oxygen (pO2 < 5 mmHg), addressing the primary failure mode of conventional Type II photosensitizers in hypoxic microenvironments.
• • Transient absorption spectroscopy reveals a long-lived charge-separated state (lifetime > 1 μs) after co-assembly, enabling efficient electron transfer to water. This charge separation efficiency is critical for sustaining ·OH flux under anoxic conditions, where oxygen-reduction pathways are suppressed.
• • In vitro photocytotoxicity assays show IC50 values below 10 μM under severe anoxia (pO2 < 1 mmHg), comparable to normoxic conditions. This potency translates to a therapeutic window that could overcome hypoxia-induced resistance in solid tumors.
• • In vivo mouse models demonstrate significant tumor growth inhibition (>80% tumor volume reduction) with minimal systemic toxicity, validating the clinical potential of oxygen-independent PDT for hypoxic tumors.