Radiotherapy (RT) is hampered by the limited oxygen in tumors, which could be potentiated via reprogramming the oxygen metabolism and increasing the oxygen utilization efficiency. Herein, a metal-phenolic nanosensitizer (Hf-PSP-DTC@PLX) was integrated via an acid-sensitive hydrogen sulfide (H2 S) donor (polyethylene glycol-co-polydithiocarbamates, PEG-DTC) and a hafnium-chelated polyphenolic semiconducting polymer (Hf-PSP) in an amphiphilic polymer (poloxamer F127, PLX). Hf-PSP-DTC@PLX elicited a high imaging performance for precise RT and generated H2 S to reduce the cellular oxygen consumption rate via mitochondrial respiration inhibition, which reprogrammed the oxygen metabolism for improvement of the tumor oxygenation. Then, Hf-sensitization could fully utilize the well-preserved oxygen to intensify RT efficacy and activate immunogenicity. Such a synergistic strategy for improvement of oxygenation and oxygen utilization would have great potential in optimizing oxygen-dependent therapeutics.
Keywords: Hydrogen Sulfide; Immunogenicity; Polyphenols; Radiotherapy; Reprogrammed Oxygen Metabolism; Semiconducting Polymers.
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