期刊
ACS NANO
卷 16, 期 4, 页码 5597-5614出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.1c10450
关键词
hydrogen therapy; O-2 elevation; yolk-shell nanostructure; multimodal imaging; synergistic therapy; malignant melanoma
类别
资金
- National Natural Science Foundation of China Project [81872493, 81803151, 22174123]
- Key University Science Research Project of Jiangsu Province [21KJA350003]
- Public Experimental Research Center of Xuzhou Medical University
Hydrogen therapy is an emerging therapeutic strategy in anticancer medicine, but the challenges of stable hydrogen storage and efficient delivery hinder its development. In this study, a smart yolk-shell nanoplatform was designed to overcome these challenges and enhance the efficacy of photodynamic therapy through hydrogen release, increased reactive oxygen species generation, and ameliorated hypoxic conditions.
Hydrogen therapy, an emerging therapeutic strategy, has recently attracted much attention in anticancer medicine. Evidence suggests that hydrogen (H-2) can selectively reduce intratumoral overexpressed hydroxyl radicals (center dot OH) to break the redox homeostasis and thereby lead to redox stress and cell damage. However, the inability to achieve stable hydrogen storage and efficient hydrogen delivery hinders the development of hydrogen therapy. Furthermore, oxygen (O-2) deficiency in the tumor microenvironment (TME) and the electron-hole separation inefficiency in photosensitizers have severely limited the efficacy of photodynamic therapy (PDT). Herein, a smart PdH@MnO2/Ce6@HA (PHMCH) yolk-shell nanoplatform is designed to surmount these challenges. PdH tetrahedrons combine stable hydrogen storage and high photothermal conversion efficiency of palladium (Pd) nanomaterials with near-infrared-controlled hydrogen release. Subsequently, the narrow bandgap semiconductor manganese dioxide (MnO2) and the photosensitizer chlorin e6 (Ce6) are introduced into the PHMCH nanoplatform. Upon irradiation, the staggered energy band edges in heterogeneous materials composed of MnO2 and Ce6 can efficiently facilitate electron-hole separation for increasing singlet oxygen (O-1(2)). Moreover, MnO2 nanoshells generate O-2 in TME for ameliorating hypoxia and further improving O-2-dependent PDT. Finally, the hyaluronic acid-modified PHMCH nanoplatform shows negligible cytotoxicity and selectively targets CD44-overexpressing melanoma cells. The synergistic antitumor performance of the H-2-mediated gas therapy combined with photothermal and enhanced PDT can explore more possibilities for the design of gas-mediated cancer therapy.
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