Department of Biomaterials, College of Materials, Research Center of Biomedical Engineering of Xiamen & Key Laboratory of Biomedical Engineering of Fujian Province & Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen 361005, China.
State Key Laboratory of Applied Organic Chemistry and Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Lanzhou University, Lanzhou 730000, Gansu, China.
ACS Appl Mater Interfaces. 2021 Jul 21;13(28):32690-32702. doi: 10.1021/acsami.1c06668. Epub 2021 Jul 7.
The synergistic nanotheranostics of reactive oxygen species (ROS) augment or phototherapy has been a promising method within synergistic oncotherapy. However, it is still hindered by sophisticated design and fabrication, lack of a multimodal synergistic effect, and hypoxia-associated poor photodynamic therapy (PDT) efficacy. Herein, a kind of porous shuttle-shape platinum (IV) methylene blue (Mb) coordination polymer nanotheranostics-loaded 10-hydroxycamptothecin (CPT) is fabricated to address the abovementioned limitations. Our nanoreactors possess spatiotemporally controlled O self-supply, self-sufficient singlet oxygen (O), and outstanding photothermal effect. Once they are taken up by tumor cells, nanoreactors as a cascade catalyst can efficiently catalyze degradation of the endogenous hydrogen peroxide (HO) into O to alleviate tumor hypoxia. The production of O can ensure enhanced PDT. Subsequently, under both stimuli of external red light irradiation and internal lysosomal acidity, nanoreactors can achieve the on-demand release of CPT to augment mitochondrial ROS and highly efficient tumor ablation via phototherapy. Moreover, under the guidance of near-infrared (NIR) fluorescent imaging, our nanoreactors exhibit strongly synergistic potency for treatment of hypoxic tumors while reducing damages against normal tissues and organs. Collectively, shuttle-shape platinum-coordinated nanoreactors with augmented ROS capacity and enhanced phototherapy efficiency can be regarded as a novel tumor theranostic agent and further promote the research of synergistic oncotherapy.
活性氧 (ROS) 的协同纳米诊疗增强或光疗一直是协同肿瘤治疗中很有前途的方法。然而，它仍然受到复杂设计和制造、缺乏多模态协同效应以及与缺氧相关的不良光动力疗法 (PDT) 疗效的限制。在此，我们制备了一种负载 10-羟基喜树碱 (CPT) 的多孔梭形铂 (IV) 亚甲基蓝 (Mb) 配位聚合物纳米诊疗剂来解决上述问题。我们的纳米反应器具有时空可控的 O 自供、自足的单线态氧 (O) 和出色的光热效应。一旦被肿瘤细胞摄取，纳米反应器作为级联催化剂可以有效地催化内源性过氧化氢 (HO) 降解为 O，以减轻肿瘤缺氧。O 的产生可以确保增强 PDT。随后，在外部红光照射和内部溶酶体酸度的双重刺激下，纳米反应器可以按需释放 CPT，通过光疗来增加线粒体 ROS 并实现高效的肿瘤消融。此外，在近红外 (NIR) 荧光成像的指导下，我们的纳米反应器在减轻对正常组织和器官的损伤的同时，对缺氧肿瘤表现出强烈的协同治疗效果。总的来说，具有增强的 ROS 能力和增强的光疗效率的梭形铂配位纳米反应器可以被视为一种新型的肿瘤治疗剂，并进一步促进协同肿瘤治疗的研究。
