Oxidative stress-augmented Cu-doped hollow mesoporous carbon nanozyme for photothermal/photodynamic synergistic therapy

Photodynamic therapy (PDT) has witnessed remarkable progress in recent years owing to its specific properties. Given that the antioxidation system of tumor microenvironment (TME) adversely affects treatment outcomes, powerful TME modulators can significantly resolve the limitation of PDT. Herein, we developed a PEG-modified Cu²⁺-doped hollow mesoporous carbon nanozyme (CHC-PEG) and loaded insoluble photosensitizer IR780 into its pores and cavities to construct the multifunctional nano-system IR780/CHCP. CHC-PEG nanozyme could perform photothermal therapy (PTT) effect and protect IR780 from aggregation-caused quenching (ACQ) effect, while exerting peroxidase (POD)-mimetic activity and the ability of consuming glutathione (GSH) to achieve oxidative stress-augmented PDT effect. When exposed to near-infrared (NIR) light, IR780 was stimulated to produce singlet oxygen (¹O₂) and CHC-PEG could increase the temperature of TME to exert stronger POD-mimetic activity for producing more hydroxyl radicals (OH), therefore the IR780/CHCP nano-system exhibited remarkable tumor growth inhibition. Benefited by the enhanced synergistic effect, IR780/CHCP exhibited remarkable in vivo tumor growth inhibition, with the tumor inhibition rate of 93 %, and had no significant effect on major organs. Above all, IR780/CHCP could resist the antioxidant system in TME to enhance the level of oxidative stress, thereby enabling effective anti-tumor therapy. This study introduced a novel strategy to effectively promote the synergistic PTT/PDT effect by the enhanced oxidative stress.