Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Material Sciences and Chemical Engineering, Harbin Engineering University, Harbin 150001, P. R. China.
MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of Chemistry and Chemical Engineering & Key Laboratory of Micro-Systems and Micro-Structures, Ministry of Education, Harbin Institute of Technology, 150001 Harbin, P. R. China.
ACS Appl Mater Interfaces. 2020 Nov 25;12(47):52479-52491. doi: 10.1021/acsami.0c17923. Epub 2020 Nov 16.
The development of near-infrared (NIR) laser triggered phototheranostics for multimodal imaging-guided combination therapy is highly desirable. However, multiple laser sources, as well as inadequate therapeutic efficacy, impede the application of phototheranostics. Here, we develop an all-in-one theranostic nanoagent PEGylated DCNP@DMSN-MoO NPs (DCDMs) with a flower-like structure fabricated by coating uniformly sized down-conversion nanoparticles (DCNPs) with dendritic mesoporous silica (DMSN) and then loading the ultrasmall oxygen-deficient molybdenum oxide nanoparticles (MoO NPs) inside through an electrostatic interaction. Owing to the doping of Nd ions, when excited by an 808 nm laser, DCNPs emit bright NIR-II emissions (1060 and 1300 nm), which have characteristic high spatial resolution and deep tissue penetration. In terms of treatment, MoO NPs could be specifically activated by excessive hydrogen peroxide (HO) in the tumor microenvironment, thus generating O the Russell mechanism. In addition, the excessive glutathione (GSH) in the tumor cells could be depleted through the Mo-mediated redox reaction, thus effectively decreasing the antioxidant capacity of tumor cells. Importantly, the excellent photothermal properties (photothermal conversion efficiency of 51.5% under an 808 nm laser) synergistically accelerate the generation of O. This cyclic redox reaction of molybdenum indeed ensured the high efficacy of tumor-specific therapy, leaving the normal tissues unharmed. MoO NPs could also efficiently catalyze tumor endogenous HO into a considerable amount of O in an acidic tumor microenvironment, thus relieving hypoxia in tumor tissues. Moreover, the computed tomography (CT) and -weighted magnetic resonance imaging (MRI) effect from Gd and Y ions make DCNPs act as a hybrid imaging agent, allowing comprehensive analysis of tumor lesions. Both and experiments validate that such an "all-in-one" nanoplatform possesses desirable anticancer abilities under single laser source irradiation, benefiting from the NIR-II fluorescence/CT/MR multimodal imaging-guided photothermal/chemodynamic synergistic therapy. Overall, our strategy paves the way to explore other noninvasive cancer phototheranostics.
近红外（NIR）激光触发光热治疗用于多模态成像引导的联合治疗的发展是非常可取的。然而，多个激光源以及不足的治疗效果阻碍了光热治疗的应用。在这里，我们开发了一种具有花状结构的一体化治疗纳米制剂 PEGylated DCNP@DMSN-MoO NPs（DCDMs），该制剂由均匀尺寸的下转换纳米粒子（DCNPs）涂覆树枝状介孔硅（DMSN）制成，然后通过静电相互作用将超小的缺氧氧化钼纳米粒子（MoO NPs）装载在内。由于掺杂了 Nd 离子，当用 808nm 激光激发时，DCNPs 会发出明亮的 NIR-II 发射（1060 和 1300nm），具有特征的高空间分辨率和深组织穿透性。在治疗方面，MoO NPs 可以被肿瘤微环境中过量的过氧化氢（HO）特异性激活，从而产生 O 通过 Russell 机制。此外，肿瘤细胞中的过量谷胱甘肽（GSH）可以通过 Mo 介导的氧化还原反应耗尽，从而有效降低肿瘤细胞的抗氧化能力。重要的是，优异的光热性能（在 808nm 激光下的光热转换效率为 51.5%）协同加速 O 的产生。这种钼的循环氧化还原反应确实确保了肿瘤特异性治疗的高效性，而对正常组织没有伤害。MoO NPs 还可以在酸性肿瘤微环境中有效地将肿瘤内源性 HO 催化为大量的 O，从而缓解肿瘤组织的缺氧。此外，来自 Gd 和 Y 离子的计算机断层扫描（CT）和加权磁共振成像（MRI）效应使 DCNPs 充当混合成像剂，允许对肿瘤病变进行全面分析。和 实验均验证了，在单一激光源照射下，这种“一体化”纳米平台具有令人满意的抗癌能力，这得益于 NIR-II 荧光/CT/MR 多模态成像引导的光热/化学动力学协同治疗。总的来说，我们的策略为探索其他非侵入性癌症光热治疗铺平了道路。
