Continuous O ₂ /H ₂ O ₂ -Evolving Hollow Manganese Ferrite Nanocomposite for Cancer Synergistic Enhanced Chemodynamic/Photothermal/Starvation Therapy

Chemodynamic therapy (CDT) holds significant promise for tumor-selective treatment; however, its therapeutic performance is frequently hampered due to the insufficient endogenous hydrogen peroxide (H₂O₂) 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 H₂O₂, inducing tumor starvation while generating additional H₂O₂ for the Fenton reaction. Simultaneously, Mn²⁺ catalyzes H₂O₂ decomposition to produce O₂, which further promotes GOx-mediated glucose oxidation and sustains the cascade catalytic reaction. The self-supplied H₂O₂ and O₂ effectively enhance the dual catalytic centers (Fe³⁺/Mn²⁺)-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 H₂O₂/O₂ generation and photothermal amplification. This breakthrough provides a novel nanoplatform and promising conceptual advancement for enhanced multimodal tumor therapy.