Two-dimensional persistent luminescence "optical battery" for autophagy inhibition-augmented photodynamic tumor nanotherapy
Two-dimensional persistent luminescence "optical battery" for autophagy inhibition-augmented photodynamic tumor nanotherapy
复制标题
用于自噬抑制增强光动力肿瘤纳米疗法的二维持久发光“光学电池”
DOI：
10.1016/j.nantod.2021.101362
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发表时间：
2022-02-01
期刊：
影响因子：
17.4
通讯作者：
Feng, Wei
中科院分区：
文献类型：
--
作者：
Chang, Meiqi;Dai, Xinyue;Feng, Wei
针对传统光动力学疗法（PDT）需要长时间外照射的关键问题，本研究将二维CaAl 2 O 4：Eu，Nd持续发光纳米片（CAO PLNS）与具有靶向作用的光敏剂维替泊芬（verteporfin）合理结合，构建了一种独特的免照射PDT纳米系统。2D CAO PLNS用作内部“光学电池”，用于连续输出细胞毒性单线态氧（O-1（2））。值得注意的是，除了触发癌细胞凋亡之外，O-1（2）诱导的细胞自噬的特征由于源自溶酶体去功能化的自噬流下游的阻断而从促存活变为促死亡。具有细胞靶向功能的2D PDT纳米系统产生的O-1（2）激活了线粒体自噬-自噬双重自我保护通路，随后自噬体和线粒体自噬体的过量产生导致了超负荷溶酶体的形成。此外，Nd 3+离子与磷酸盐的强配位能力破坏了溶酶体磷蛋白膜结构。这种2D PDT纳米系统介导的自噬抑制将放大细胞凋亡主导的治疗功效。体外和体内试验结果均肯定了自噬抑制致敏PDT的抗肿瘤作用。这项工作强调了2D持续发光PDT纳米平台诱导的促死亡自噬在癌症治疗中的重要作用。(C)2021爱思唯尔出版
Aiming at solving the critical issue of traditional photodynamic therapy (PDT) that requires long-lasting external light irradiation, in this work, we develop a distinct irradiation-free PDT nanosystem based on the rational combination of two dimensional (2D) CaAl2O4:Eu,Nd persistent luminescence nanosheets (CAO PLNSs) and photosensitizer verteporfin with mitochondrial-targeting function. 2D CAO PLNSs are served as internal "optical battery" for the continuous output of cytotoxic singlet oxygen (O-1(2)). Notably, in addition to triggering cancer-cell apoptosis, the characteristic of O-1(2)-induced cell autophagy changes from pro-survival to pro-death due to the blockage downstream of autophagy flow originating from lysosomal de-functionalization. The O-1(2) generated by 2D PDT nanosystem with mitochondrial-targeting feature activates mitophagy-autophagy dual self-protective pathways, and the subsequent excessive production of autophagosome and mitophagosome causes the formation of overloaded lysosome. Additionally, the strong coordination ability of Nd3+ ions with phosphates disrupts the lysosomal phosphoprotein membrane structure. This 2D PDT nanosystem-mediated autophagy inhibition would amplify apoptosis-dominant therapeutic efficacy. Both in vitro and in vivo assay results positively affirm the antineoplastic effect of autophagy inhibition-sensitized PDT. This work emphasizes the considerable role of 2D persistent luminescence PDT nanoplatform-induced pro-death autophagy in cancer treatment. (C) 2021 Published by Elsevier Ltd.