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A Bacteriochlorin‐Based Metal–Organic Framework Nanosheet Superoxide Radical Generator for Photoacoustic Imaging‐Guided Highly Efficient Photodynamic Therapy

机译:基于细菌氯霉素的金属-有机骨架纳米片超氧化物自由基发生器用于光声成像引导的高效光动力疗法

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摘要

Hypoxic tumor microenvironment is the bottleneck of the conventional photodynamic therapy (PDT) and significantly weakens the overall therapeutic efficiency. Herein, versatile metal–organic framework (MOF) nanosheets (DBBC‐UiO) comprised of bacteriochlorin ligand and Hf6(µ3‐O)4(µ3‐OH)4 clusters to address this tricky issue are designed. The resulting DBBC‐UiO enables numerous superoxide anion radical (O2 −•) generation via a type I mechanism with a 750 nm NIR‐laser irradiation, part of which transforms to high toxic hydroxyl radical (OH•) and oxygen (O2) through superoxide dismutase (SOD)‐mediated catalytic reactions under severe hypoxic microenvironment (2% O2), and the partial recycled O2 enhances O2 −• generation. Owing to the synergistic radicals, it realizes advanced antitumor performance with 91% cell mortality against cancer cells in vitro, and highly efficient hypoxic solid tumor ablation in vivo. It also accomplishes photoacoustic imaging (PAI) for cancer diagnosis. This DBBC‐UiO, taking advantage of superb penetration depth of the 750 nm laser and distinct antihypoxia activities, offers new opportunities for PDT against clinically hypoxic cancer.
机译:缺氧性肿瘤微环境是常规光动力疗法(PDT)的瓶颈,严重削弱了整体治疗效率。本文设计了由细菌绿素配体和Hf6(µ3-O)4(µ3-OH)4簇组成的通用金属-有机骨架(MOF)纳米片(DBBC-UiO),以解决这一棘手的问题。产生的DBBC‐UiO通过具有750 nm NIR激光辐照的I型机制,能够产生大量超氧阴离子自由基(O2 -•),其中一部分转化为高毒性羟基自由基(OH•)在严重缺氧的微环境(2%O2)下通过超氧化物歧化酶(SOD)介导的催化反应产生氧气(O2),部分再循环的O2增强O2 -•的产生。由于具有协同作用的自由基,它实现了先进的抗肿瘤性能,体外对癌细胞的细胞死亡率为91%,体内高效低氧实体瘤消融术。它还可以完成光声成像(PAI)以进行癌症诊断。这种DBBC-UiO利用750 nm激光的出色穿透深度和独特的抗缺氧活性,为PDT抗临床缺氧性癌症提供了新的机会。

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