Cao Fangling, Shao Weiyang, Liu Yuanyuan, Lei Wenwen, Pang Shuqin, Zhou Shuyao, Xu Keming, Zhong Wenying
Department of Chemistry, China Pharmaceutical University, Nanjing 210009, China.
Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing 210009, China.
ACS Appl Mater Interfaces. 2025 Jun 11;17(23):33633-33647. doi: 10.1021/acsami.5c06254. Epub 2025 May 27.
Chemodynamic therapy (CDT) has emerged as a transformative paradigm in the realm of reactive oxygen species (ROS)-mediated cancer therapies. However, the lack of endogenous hydrogen peroxide (HO) in tumors and the low catalytic efficiency of traditional Fenton catalysts limit the therapeutic effect of CDT. Herein, an injectable nanocomposite hydrogel (HA-DOPA/W-POM/-S-S-PEG@GOx) based on the hyaluronic acid-dopamine (HA-DOPA) matrix is designed to deliver tungsten-based polyoxometalates (W-POM) and peptide nanomicelles (-S-S-PEG@GOx) for achieving cascade-catalytic and photothermal dually enhanced CDT. Upon tumor cell uptake, -S-S-PEG@GOx specifically responds to endogenous glutathione and disassembles to release glucose oxidase (GOx), which catalyzes the oxidation of glucose to produce HO. On the one hand, W-POM functions as peroxidase-like nanozymes to convert HO into a hydroxyl radical (OH) under the aid of GOx, enhancing the efficacy of CDT through cascade-catalytic reactions (i.e., glucose to HO to OH). On the other hand, W-POM acts as a photothermal therapy agent, generating mild heat under near-infrared laser irradiation to achieve photothermal-enhanced CDT. This cascade-catalytic and photothermal dually enhanced CDT triggers an intracellular ROS storm, leading to apoptosis and ferroptosis of tumor cells. Importantly, in situ administration of HA-DOPA/W-POM/-S-S-PEG@GOx alongside laser irradiation showcases enhanced antitumor efficacy and satisfactory biocompatibility in vivo, which holds great potential for the development of functional nanomedicine toward targeted tumor therapy.
化学动力疗法（CDT）已成为活性氧（ROS）介导的癌症治疗领域中一种变革性的治疗模式。然而，肿瘤内源性过氧化氢（HO）的缺乏以及传统芬顿催化剂的低催化效率限制了CDT的治疗效果。在此，基于透明质酸 - 多巴胺（HA - DOPA）基质设计了一种可注射的纳米复合水凝胶（HA - DOPA/W - POM/-S - S - PEG@GOx），用于递送钨基多金属氧酸盐（W - POM）和肽纳米胶束（-S - S - PEG@GOx），以实现级联催化和光热双重增强的CDT。在肿瘤细胞摄取后，-S - S - PEG@GOx特异性响应内源性谷胱甘肽并分解以释放葡萄糖氧化酶（GOx），后者催化葡萄糖氧化产生HO。一方面，W - POM作为类过氧化物酶纳米酶，在GOx的辅助下将HO转化为羟基自由基（OH），通过级联催化反应（即葡萄糖到HO再到OH）增强CDT的疗效。另一方面，W - POM作为光热治疗剂，在近红外激光照射下产生温和热量以实现光热增强的CDT。这种级联催化和光热双重增强的CDT引发细胞内ROS风暴，并导致肿瘤细胞凋亡和铁死亡。重要的是，HA - DOPA/W - POM/-S - S - PEG@GOx与激光照射联合原位给药在体内显示出增强的抗肿瘤疗效和令人满意的生物相容性，这为开发用于靶向肿瘤治疗的功能性纳米药物具有巨大潜力。
