Progressive-composition-transformation-induced enhanced hyperthermia-based nanozyme towards long-lasting and complete therapy of cancer

作者：Wenlong Zhang, Di Sun, Bin Yang, Jiaqi Liu, Yilin Yuan, Dezhuang Li, Yuliang Sun, Guoqiang Guan, Yanli Liu, Dapeng Wu, Hong Liao, Juntang Lin, Junqing Hu · 发表于：Chemical Engineering Journal · 年份：2025 · DOI：10.1016/j.cej.2025.160645 · 被引用次数：4 · 研究领域：Nanoplatforms for cancer theranostics、Advanced Nanomaterials in Catalysis、Nanocluster Synthesis and Applications

The biggest bottleneck for nanozymes-initiated chemodynamic therapy (CDT) of cancer is that nanozymes cannot continuously yield hydroxyl radicals towards lasting CDT, given their diffusion and clearance from tumor tissues as well as lower tumor accumulation. Herein, based on a composition-transformable bovine serum albumin (BSA) modified Cu/CuFe 2 O 4 (CCFOB) nanozyme , we present a novel avenue to achieve lasting CDT. This CCFOB nanozyme with peroxidase (POD)-like activity and glutathione depletion ability not only amplifies oxidative stress for effective CDT, but exhibits magnetic targeting and imaging-guided simultaneous photothermal therapy (PTT)/magnetic hyperthermia therapy (MHT)/chemotherapy. Contrasting with traditional cognition, we clarify Cu/CuFe 2 O 4 is actually composed of CuFe 2 O 4 nanocrystal clusters and Cu nanospheres . Attractively, for the first time, it is demonstrated that in microenvironment of residual tumors, CCFOB nanozyme could be progressively transformed into BSA modified Cu 2 O/Cu/CuFe 2 O 4 , which renders CCFOB to be a Cu + reservoir to continuingly produce high-reactivity Cu + . Such continuing production of Cu + grants CCFOB nanozyme increasingly enhanced POD-like activity for lasting CDT despite its diffusion and clearance from tumor tissues. Thus, a programmed synergistic therapy strategy starting with high-intensity PTT/MHT/chemotherapy/CDT to eradicate larger tumors, followed by lasting CDT to eliminate residual tumors and prevent tumor ...