Tang Jiadong, Li Chi, Ma Wenjie, Ba Zhengnuo, Hu Zhubin, Willner Itamar, Wang Chen
School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, China.
State Key Laboratory of Precision Spectroscopy, School of Physics and Electronic Science, East China Normal University, Shanghai, 200241, China.
Angew Chem Int Ed Engl. 2025 Jun 2;64(23):e202503485. doi: 10.1002/anie.202503485. Epub 2025 Apr 1.
Pd-based intracellular catalysis has attracted increasing interest in modulating biological processes or disease treatment. The unsatisfactory catalytic efficiency arising from limited active sites and poor water solubility of palladium nanoparticles (Pd NPs) and their "always on" catalytic activities pose, however, significant limitations. Herein, we develop a high-performance nanocomposite based on ultrafine Pd NPs confined within molecular cages, and incorporated with glucose oxidase (GOx) and AS1411 aptamer-modified hyaluronic acid (HA). The cage-confined strategy enables facile synthesis of ultrafine Pd NPs with more accessible active sites, significantly improving the catalytic activities of Pd NPs for enhanced bioorthogonal catalysis. Importantly, the nanocomposite exhibits targeting ability and activatable activity in response to both the acidic pH and hyaluronidase overexpressed in the tumor environment, enabling selective drug synthesis. Besides, it features CAT-, OXD-, and GPx-like activities, promoting reactive oxygen species (ROS) generation and intracellular GSH depletion to elevate oxidative stress for enhanced therapy. The cage-confined configuration makes it possible to establish metal-based intracellular catalytic systems with high performance, enabling the synthesis of desired molecules for effective disease theranostics.
基于钯的细胞内催化在调节生物过程或疾病治疗方面引起了越来越多的关注。然而，钯纳米颗粒（Pd NPs）活性位点有限和水溶性差导致的催化效率不理想以及它们“持续开启”的催化活性构成了重大限制。在此，我们开发了一种基于分子笼内限域的超细Pd NPs的高性能纳米复合材料，并将其与葡萄糖氧化酶（GOx）和AS1411适配体修饰的透明质酸（HA）相结合。笼内限域策略能够轻松合成具有更多可及活性位点的超细Pd NPs，显著提高Pd NPs的催化活性以增强生物正交催化。重要的是，该纳米复合材料在肿瘤环境中对酸性pH和过表达的透明质酸酶均表现出靶向能力和可激活活性，实现选择性药物合成。此外，它具有类CAT、类OXD和类GPx活性，促进活性氧（ROS）生成和细胞内谷胱甘肽（GSH）消耗以提高氧化应激从而增强治疗效果。笼内限域结构使得建立高性能的基于金属的细胞内催化系统成为可能，能够合成所需分子用于有效的疾病诊疗。
