Jiang Xiang, Sun Lina, Zhao Yuewu, Lu Zhiyong, He Xuan, Xiang Ying, Liu Xingzhu, Wang Jine, Pei Renjun
CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
College of Materials Science and Engineering, Hohai University, Nanjing 210098, China.
ACS Nano. 2025 Aug 5;19(30):27351-27369. doi: 10.1021/acsnano.5c05276. Epub 2025 Jul 24.
Sonodynamic therapy (SDT) has demonstrated promising potential in the treatment of tumors and has attracted widespread attention. The majority of sound-sensitive materials developed to date have been categorized as oxygen-dependent type II sonosensitizers (SSs), which are susceptible to tumor hypoxia and significantly limit their efficacy. In this study, highly active porphyrin-based metal-organic frameworks (Yb-TCPP PMOF) with type I/II SDT dual actions were constructed by regulating the electron transfer process between metal nodes and ligands, which can produce multiple reactive oxygen species (ROS) such as O, O, and •OH. After that, the energy level barrier of triplet SSs was reduced by in situ loading of Au nanoparticles with the electronic grab-transport (EGT) effect, and the ROS yield was increased by accelerating the electron transport. Intriguingly, the successful construction of Au/Yb-TCPP not only produced abundant oxygen vacancy defects but also reduced the band gap, which effectively facilitated the electron-hole separation of SSs and further improved the SDT efficiency by inhibiting its recombination process. Furthermore, we also found that these ultrasmall Au nanoparticles in the MOF structure can act as catalase and undergo cascade reactions with glucose oxidase and obtain a self-producing oxygen circulation system (Au/Yb-TCPP@GOx) by reducing glucose through the coordination of nanoenzyme and bioenzyme. This not only significantly alleviates the hypoxia state of tumors but also has a starvation effect on tumor cells. Finally, it was verified at the levels of tumor cells and mice that Au/Yb-TCPP@GOx can effectively inhibit tumors through the dual effects of enhanced type I and type II SDT, as well as the starvation effect. The composite materials constructed showed a multisynergistic enhancement effect, which has guiding significance for improving electron transport, alleviating tumor hypoxia, enhancing ROS yield, and constructing starvation treatment strategies.
声动力疗法（SDT）在肿瘤治疗中已展现出有前景的潜力，并引起了广泛关注。迄今为止开发的大多数声敏材料都被归类为依赖氧气的II型声敏剂（SSs），它们易受肿瘤缺氧影响，显著限制了其疗效。在本研究中，通过调节金属节点与配体之间的电子转移过程，构建了具有I/II型SDT双重作用的高活性卟啉基金属有机框架（Yb-TCPP PMOF），其可产生多种活性氧（ROS），如O、O和•OH。之后，通过具有电子捕获-传输（EGT）效应的金纳米颗粒原位负载，降低了三线态SSs的能级势垒，并通过加速电子传输提高了ROS产量。有趣的是，Au/Yb-TCPP的成功构建不仅产生了大量氧空位缺陷，还减小了带隙，有效促进了SSs的电子-空穴分离，并通过抑制其复合过程进一步提高了SDT效率。此外，我们还发现MOF结构中的这些超小金纳米颗粒可作为过氧化氢酶，与葡萄糖氧化酶发生级联反应，并通过纳米酶与生物酶的协同作用还原葡萄糖，从而获得自供氧气循环系统（Au/Yb-TCPP@GOx）。这不仅显著缓解了肿瘤的缺氧状态，还对肿瘤细胞产生饥饿效应。最后，在肿瘤细胞和小鼠水平上验证了Au/Yb-TCPP@GOx可通过增强I型和II型SDT的双重作用以及饥饿效应有效抑制肿瘤。所构建的复合材料表现出多协同增强效应，这对改善电子传输、缓解肿瘤缺氧、提高ROS产量以及构建饥饿治疗策略具有指导意义。
