Cun Fei, Chen Jie, Li Hanxue, Kou Yufang, Wang Meiyan, Li Xiaomin, Chen Hui, Kong Jilie
Department of Chemistry, Fudan University, Shanghai, 200438, China.
411 Hospital, School of Medicine, Shanghai University, Shanghai, 200444, China.
Adv Sci (Weinh). 2025 Jul;12(28):e2502688. doi: 10.1002/advs.202502688. Epub 2025 May 11.
While massive studies are focused on platinum (Pt)-based nanozyme for antitumor therapies, their therapeutic efficiency is deficient due to the weak catalytic activity in the highly complex tumor microenvironment. Herein, mesoporous gold nanospheres confined platinum nanoclusters (MGNSs@Pt) as robust hydroxyl radical and oxygen nanogenerators are achieved for multimodal therapies. Benefiting from the confinement effect of the mesopores in the MGNSs, the Pt nanoclusters (Pt NCs) demonstrate enhanced stability and catalytic activity, with a catalytic constant (K) of 1.42 × 10 s, which is 2 and 5 orders magnitude higher than K values of Pt-decorated non-porous gold nanoparticles and pure Pt NCs respectively. Density functional theory (DFT) calculations reveal the proper interaction of intermediates contributes to the ultra-high catalytic activity of MGNSs@Pt. Meanwhile, owing to the local surface plasmon resonance (LSPR) effect in the second near-infrared (NIR-II) bio-window of MGNSs, the nanozymes exhibited high photothermal conversion efficiency up to 43.4%, which enhanced the nanocatalytic damage on cancer cells. This process can induce robust oxidative stress and oxygenation within the tumor, thereby activating the apoptosis pathway for tumor eradication by mitochondrial dysfunction, cell membrane disruption, HIF-1α downregulation as well as caspase 3 activation, which pave the way for multimodal and effective cancer treatment.
尽管大量研究聚焦于基于铂（Pt）的纳米酶用于抗肿瘤治疗，但由于其在高度复杂的肿瘤微环境中催化活性较弱，治疗效率低下。在此，我们制备了介孔金纳米球限域铂纳米簇（MGNSs@Pt）作为强大的羟基自由基和氧纳米发生器用于多模态治疗。得益于MGNSs中介孔的限域效应，铂纳米簇（Pt NCs）表现出增强的稳定性和催化活性，催化常数（K）为1.42×10 s，分别比铂修饰的无孔金纳米颗粒和纯Pt NCs的K值高2个和5个数量级。密度泛函理论（DFT）计算表明中间体之间适当的相互作用有助于MGNSs@Pt的超高催化活性。同时，由于MGNSs在第二近红外（NIR-II）生物窗口中的局域表面等离子体共振（LSPR）效应，纳米酶表现出高达43.4%的高光热转换效率，增强了对癌细胞的纳米催化损伤。这一过程可在肿瘤内诱导强烈的氧化应激和氧合作用，从而通过线粒体功能障碍、细胞膜破坏、HIF-1α下调以及半胱天冬酶3激活激活肿瘤根除的凋亡途径，为多模态有效癌症治疗铺平了道路。
