Mild-temperature responsive nanocatalyst for controlled drug release and enhanced catalytic therapy

Owing to the advantages of the in situ production of toxic agents through catalytic reactions, nanocatalytic therapy has arisen as a highly potential strategy for cancer therapeutics in recent years. However, the insufficient amount of endogenous hydrogen peroxide (H₂O₂) in the tumor microenvironment commonly limits their catalytic efficacy. Here, we employed carbon vesicle nanoparticles (CV NPs) with high near-infrared (NIR, 808 nm) photothermal conversion efficiency as carriers. Ultrafine platinum iron alloy nanoparticles (PtFe NPs) were grown in situ on the CV NPs, where the highly porous nature of the resultant CV@PtFe NPs was employed to encapsulate a drug, β-lapachone (La), and phase-change material (PCM). As a multifunctional nanocatalyst CV@PtFe/(La-PCM) NPs can exhibit a NIR-triggered photothermal effect and activate cellular heat shock response, which upregulates the downstream NQO1 via HSP70/NQO1 axis to facilitate bio-reduction of the concurrently melted and released La. Moreover, sufficient oxygen (O₂) is supplied by CV@PtFe/(La-PCM) NPs catalyzed at the tumor site to reinforce the La cyclic reaction with abundant H₂O₂ generation. This promotes the bimetallic PtFe-based nanocatalysis, which breaks H₂O₂ down into highly toxic hydroxyl radicals (•OH) for catalytic therapy. Our results show that this multifunctional nanocatalyst can be used as a versatile synergistic therapeutic agent with NIR-enhanced nanocatalytic tumor therapy by tumor-specific H₂O₂ amplification and mild-temperature photothermal therapy, which holds promising potential for targeted cancer treatment. Statement of significance: We present a multifunctional nanoplatform with mild-temperature responsive nanocatalyst for controlled drug release and enhanced catalytic therapy. This work aimed at not only reduce the damage to normal tissues caused by photothermal therapy, but also improves the efficiency of nanocatalytic therapy by stimulating endogenous H₂O₂ production through photothermal heat. In vitro and in vivo confirmed that CV@PtFe/(La-PCM) NPs exhibited powerful and overall antitumor effects. This formulation may provide an alternative strategy for the development of the mild- photothermal enhanced nanocatalytic therapy effect in solid tumor.