Wang Yue, Liu Sihui, Lu Shengze, Cheng Danling, Fan Yongliang, Li Jingchao, Lu Xia, Xia Jindong
Department of Radiology, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China.
Department of Radiology, Fujian Medical University Union Hospital, Fuzhou 350001, China.
J Mater Chem B. 2025 Jun 25. doi: 10.1039/d5tb01218j.
Chemodynamic therapy (CDT) has been widely adopted for cancer therapy, but its efficacy is limited by some factors such as low intratumoral HO level and glutathione (GSH) scavenging in the tumor microenvironment (TME). NIR-II photothermal therapy (PTT) enhances catalytic kinetics and alleviates TME restrictions deep tissue penetration and spatiotemporally controlled hyperthermia. Herein, we report a tumor-targeted nanocomposite called SPMG by integrating bovine serum albumin (BSA)-MnO, a semiconducting polymer (SP), and glucose oxidase (GOx) to enable NIR-II-triggered PTT and enzyme-augmented CDT. The semiconducting polymer SP shows high NIR-II photothermal conversion efficiency ( = 1064 nm) to enable precision PTT through tumor-localized hyperthermia. It drives self-assembly with BSA-MnO nano-coprecipitation to form SPM, which serves as stable carrier for GOx immobilization. The resultant nanocomposites (SPMG) synergize the dual therapeutic modalities in addition to NIR-II PTT: MnO releases Mn ions for CDT Mn-catalyzed Fenton-like reaction and GOx-mediated glucose oxidation to generate endogenous HO. This cascade fuels Mn-catalyzed reaction, thus achieving self-enhanced CDT through ˙OH burst, with concurrent mild hyperthermia (≤45 °C) for amplifying enzymatic activity and tumor-specific ROS accumulation. This NIR-II light-mediated PTT-CDT combinatorial therapy enables effective treatments of subcutaneous 4T1 tumors in mouse models.
化学动力学疗法（CDT）已被广泛应用于癌症治疗，但其疗效受到一些因素的限制，如肿瘤内羟基（HO）水平较低以及肿瘤微环境（TME）中的谷胱甘肽（GSH）清除作用。近红外二区光热疗法（PTT）增强了催化动力学，并缓解了TME限制，实现了深层组织穿透和时空可控的热疗。在此，我们报告了一种名为SPMG的肿瘤靶向纳米复合材料，它通过整合牛血清白蛋白（BSA）-MnO、一种半导体聚合物（SP）和葡萄糖氧化酶（GOx），实现了近红外二区触发的PTT和酶增强的CDT。半导体聚合物SP显示出高的近红外二区光热转换效率（ = 1064 nm），通过肿瘤局部热疗实现精确的PTT。它与BSA-MnO纳米共沉淀驱动自组装形成SPM，作为固定GOx的稳定载体。所得的纳米复合材料（SPMG）除了近红外二区PTT外，还协同了两种治疗方式：MnO通过Mn催化的类芬顿反应释放Mn离子用于CDT，以及GOx介导的葡萄糖氧化以产生内源性HO。这种级联反应为Mn催化反应提供燃料，从而通过羟基自由基（˙OH）爆发实现自我增强的CDT，同时伴有轻度热疗（≤45°C）以放大酶活性和肿瘤特异性活性氧（ROS）积累。这种近红外二区光介导的PTT-CDT联合疗法能够有效治疗小鼠模型中的皮下4T1肿瘤。
