Biodegradable oxygen-producing manganese-chelated metal organic frameworks for tumor-targeted synergistic chemo/photothermal/photodynamic therapy
Biodegradable oxygen-producing manganese-chelated metal organic frameworks for tumor-targeted synergistic chemo/photothermal/photodynamic therapy
复制标题
用于肿瘤靶向协同化疗/光热/光动力治疗的可生物降解的产氧锰螯合金属有机框架
DOI：
10.1016/j.actbio.2021.10.032
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发表时间：
2022-01-02
影响因子：
9.7
通讯作者：
Dong, Chunyan
中科院分区：
文献类型：
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作者：
Feng, Lei;Chen, Mengyao;Dong, Chunyan
光动力疗法(PDT)是一种有效的非侵入性治疗策略，它可以通过激发光和光敏剂的共定位将氧转化为高细胞毒性的单线态氧(O-1(2))。然而，受低氧肿瘤微环境的影响，光动力疗法的疗效严重降低。在这里，为了克服肿瘤相关性缺氧，进一步实现肿瘤靶向化疗/光动力疗法/光热疗法(PTT)的协同作用，我们构建了一个可生物降解的产氧纳米平台(名为Ini@PM-HP)，该平台由多孔金属-有机骨架(PCN-224(Mn))、聚(ADP-核糖)聚合酶(PARP)抑制剂(Iniparib)和聚多巴胺修饰的透明质酸(HA-PDA)组成。由于HA可以与肿瘤细胞上过度表达的HA受体(簇决定簇44，CD44)特异性结合，Ini@PM-HP喜欢在静脉注射后在肿瘤部位蓄积。然后，iniparib可以在肿瘤环境(TME)中释放，从而导致DNA损伤修复功能障碍，促进细胞凋亡。同时，锰与四(4-羧基苯基)卟啉(Mn-TCPP)的络合作用可通过与内源H_2O_2反应原位生成O-2，缓解缺氧的TME，提高光催化活性。此外，由于PDA具有很高的光热转换效率，因此可以用808 nm激光来驱动PTT。体内和体外实验表明，这种纳米治疗方法使联合治疗能够对肿瘤产生巨大的抑制作用。总之，所制备的纳米平台为克服肿瘤相关的缺氧提供了一种很有前途的策略，并显示出巨大的联合治疗肿瘤的潜力。利用主动靶向、PTT、增强型PDT和PARPI的优势，这种纳米治疗方法成功地实现了化疗/光热/光动力联合治疗，同时对实体瘤有很大的抑制作用。(C)2021 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Photodynamic therapy (PDT) is an effective noninvasive therapeutic strategy that can convert oxygen to highly cytotoxic singlet oxygen (O-1(2)) through the co-localization of excitation light and photosen-sitizers. However, compromised by the hypoxic tumor microenvironment, the therapeutic efficacy of PDT is reduced seriously. Herein, to overcome tumor-associated hypoxia, and further achieve tumor-targeted synergistic chemotherapy/PDT/photothermal therapy (PTT), we have constructed a biodegrad-able oxygen-producing nanoplatform (named Ini@PM-HP), which was composed of the porous metal-organic framework (PCN-224(Mn)), the poly (ADP-ribose) polymerase (PARP) inhibitor (Iniparib), and the polydopamine-modified hyaluronic acid (HA-PDA). Since HA can specifically bind to the overexpressed HA receptors (cluster determinant 44, CD44) on tumor cell, Ini@PM-HP prefers to accumulate at the tumor site once injected intravenously. Then iniparib can be released in tumor environment (TME), thereby dysfunctioning DNA damage repair and promoting cell apoptosis. At the same time, the chelating of Mn and tetrakis(4-carboxyphenyl) porphyrin (Mn-TCPP) can generate O-2 in situ by reacting with endogenous H2O2, relieving the hypoxic TME and achieving enhanced PDT. Moreover, owing to the high photother-mal conversion efficiency of PDA, PTT can be driven by the 808 nm laser irradiation. As systematically demonstrated in vitro and in vivo, this nanotherapeutic approach enables the combined therapy with great inhibition on tumor. Overall, the as-prepared nanoplatform provide a promising strategy to over-come tumor-associated hypoxia, and shows great potential for combination tumor therapy.Statement of significanceA delicately designed biodegradable oxygen-producing nanoplatform Ini@PM-HP is constructed to achieve combination therapy of solid tumors. Taking advantage of the active-targeting, PTT, enhanced PDT and PARPi, this nanotherapeutic approach successfully enables the combined chemo/photothermal/photodynamic therapy with great inhibition of solid tumors. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.