Xiao Chu, Yiling Li, Liufang Zhang, Man Shu, Wenwu Zou, Zhenze Xie, Chang Du
Chemodynamic therapy (CDT) holds significant promise for tumor-selective treatment; however, its therapeutic performance is frequently hampered due to the insufficient endogenous hydrogen peroxide (H 2 O 2 ) and strict Fenton reaction conditions. Herein, an innovative cascade-amplified nanoreactor is synthesized through a solvothermal approach, with F127 serving as a structure-directing soft template to construct hollow manganese ferrite nanoparticles (HMF), further coated with polydopamine (HMFP) and loaded with glucose oxidase (GOx) (HMFPG). Within the tumor microenvironment, glucose is oxidized by the released GOx to form gluconic acid and H 2 O 2, inducing tumor starvation while generating additional H 2 O 2 for the Fenton reaction. Simultaneously, Mn 2+ catalyzes H 2 O 2 decomposition to produce O 2, which further promotes GOx-mediated glucose oxidation and sustains the cascade catalytic reaction. The self-supplied H 2 O 2 and O 2 effectively enhance the dual catalytic centers (Fe 3+ /Mn 2+ )-mediated Fenton and Fenton-like reactions, producing abundant ·OH radicals. Moreover, the photothermal effect of HMFP accelerates the Fenton reaction rate, establishing a positive feedback process for CDT. Both in vitro cellular and in vivo animal studies demonstrate that the integrated CDT/photothermal therapy (PTT)/starvation therapy (ST) achieves remarkable antitumor efficacy. Overall, this self-sufficient nanoplatform (HMFPG) significantly boosts CDT performance by integrating dual catalytic centers, autonomous H 2 O 2 /O 2 generation and photothermal amplification. This breakthrough provides a novel nanoplatform and promising conceptual advancement for enhanced multimodal tumor therapy.