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实现具有可控光热和催化性能的“一体化”Fe/Tm-MOFs,用于影像引导的多模式协同治疗。

Achieving a "all in one" Fe/Tm-MOFs with controllable photothermal and catalytic performance for imaging-guided multi-modal synergetic therapy.

机构信息

Ministry-of-Education Key Laboratory for the Synthesis and Application of Organic Function Molecules, Hubei University, 430062, China.

Hubei Key Laboratory of Polymer Materials, Hubei University, 430062, China.

出版信息

J Colloid Interface Sci. 2022 Oct;623:124-134. doi: 10.1016/j.jcis.2022.05.015. Epub 2022 May 9.

Abstract

Targeting excess HO in the tumor microenvironment, nanotheranostic agents for catalytic therapy are designed based on Fenton reaction, catalyzing HO into oxygen and hydroxyl radical (OH). But the catalytic efficiency in tumor microenvironment is not satisfactory. In order to solve the problem, a series of bimetallic-dual ligands metal-organic frameworks Fe/Tm-MOFs were designed, that Fe and Tm as metalions, 2-methylimidazole and trimesic acid as ligands. Due to the doped Tm in Fe/Tm-MOFs and the conjugated structures formed by two ligands, the rate of electron transfer was improved, thus promoting the generation of OH at some extent. In addition, the photothermal effect of Fe/Tm-MOFs further promotes the generation of OH, which was evidenced by the 3,3',5,5'-tetramethylbenzidine(TMB). Combining the drug loading and release capabilities of Fe/Tm-MOFs, synergetic therapy of photothermal/chemo-/catalytic therapy can be achieved. In vitro results reveal that DOX release behaviors are both pH- and thermal-responsive. In vivo anti-cancer results show that the tumors of mice almost disappeared within 10 days, which were injected with Fe/Tm-MOFs/DOX and irradiated with 808 nm for 10 min. Thus, an excellent therapeutic performance has been achieved. Besides, Fe/Tm-MOFs can serve as a multimodality bioimaging contrast agent, covering fluorescence imaging, photothermal imaging and magnetic resonance imaging. Thus, an all-in-one nanotheranostic agent is constructed, improving the catalytic efficiency and providing a novel method to design an efficient nanotheranostic agent.

摘要

针对肿瘤微环境中过量的 HO,设计了基于 Fenton 反应的纳米治疗剂用于催化治疗,将 HO 催化为氧气和羟基自由基 (OH)。但是,在肿瘤微环境中的催化效率并不令人满意。为了解决这个问题,设计了一系列双金属-双配体金属-有机骨架 Fe/Tm-MOFs,其中 Fe 和 Tm 作为金属离子,2-甲基咪唑和均苯三甲酸作为配体。由于 Fe/Tm-MOFs 中掺杂了 Tm 和两个配体形成的共轭结构,提高了电子转移速率,从而在一定程度上促进了 OH 的生成。此外,Fe/Tm-MOFs 的光热效应进一步促进了 OH 的生成,这一点可以通过 3,3',5,5'-四甲基联苯胺(TMB)得到证明。结合 Fe/Tm-MOFs 的药物负载和释放能力,可以实现光热/化疗/催化联合治疗。体外结果表明,DOX 的释放行为既对 pH 敏感又对温度敏感。体内抗癌结果表明,注射了 Fe/Tm-MOFs/DOX 并在 808nm 下照射 10 分钟的小鼠肿瘤在 10 天内几乎消失。因此,实现了优异的治疗效果。此外,Fe/Tm-MOFs 可用作多模态生物成像造影剂,涵盖荧光成像、光热成像和磁共振成像。因此,构建了一种多功能的纳米治疗剂,提高了催化效率,并为设计高效的纳米治疗剂提供了新方法。

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