期刊
ACS NANO
卷 14, 期 8, 页码 9711-9727出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.0c01350
关键词
pro-death autophagy; hypoxia relief; 3-bromopyruvate; photodynamic therapy; respiration inhibition
类别
资金
- National Natural Science Foundation of China [21774110]
- Medical Science and Technology Project of Zhejiang Province [2019PY020]
- Fundamental Research Funds for the Central Universities [2019QNA4063]
Autophagy triggered by reactive oxygen species (ROS) in photodynamic therapy (PDT) generally exhibits an anti-apoptotic effect to promote cell survival. Herein, an innovative supramolecular nanoplatform was fabricated for enhanced PDT by converting the role of autophagy from pro-survival to pro-death. The respiration inhibitor 3-bromopyruvate (3BP), which can act as an autophagy promoter and hypoxia ameliorator, was integrated into photosensitizer chlorin e6 (Ce6)-encapsulated nanoparticles to combat hypoxic tumor. 3BP could inhibit respiration by down-regulating HK-II and GAPDH expression to significantly reduce intracellular oxygen consumption rate, which could relieve tumor hypoxia for enhanced photodynamic cancer therapy. More importantly, the autophagy level was significantly elevated by the combination of 3BP and PDT determined by Western blot, immunofluorescent imaging, and transmission electron microscopy. It was very surprising that excessively activated autophagy promoted cell apoptosis, leading to the changeover of autophagy from pro-survival to pro-death. Therefore, PDT combined with 3BP could achieve efficient cell proliferation inhibition and tumor regression. Furthermore, hypoxia-inducible factor-1 alpha (HIF-1 alpha) could be down-regulated after tumor hypoxia was relieved by 3BP. Tumor metastasis could then be effectively inhibited by eliminating primary tumors and down-regulating HIF-1 alpha expression. These results provide an inspiration for future innovative approaches of cancer therapy by triggering pro-death autophagy.
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