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用于化学动力学疗法的多刺激响应性铜基金属有机框架@角蛋白药物递送系统

Multi-stimuli responsive Cu-MOFs@Keratin drug delivery system for chemodynamic therapy.

作者信息

Du Jinsong, Chen Guanping, Yuan Xinyi, Yuan Jiang, Li Li

机构信息

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences and the Affiliated Hospital, Key Laboratory of Aging and Cancer Biology of Zhejiang Province, Hangzhou Normal University, Hangzhou, China.

Jiangsu Key Laboratory of Bio-functional Materials, School of Chemistry and Materials Science, Nanjing Normal University, Nanjing, China.

出版信息

Front Bioeng Biotechnol. 2023 Feb 2;11:1125348. doi: 10.3389/fbioe.2023.1125348. eCollection 2023.

Abstract

Although the potential of metal-organic framework (MOF) nanoparticles as drug delivery systems (DDS) for cancer treatment has been established by numerous studies, their clinical applications are still limited due to relatively poor biocompatibility. We fabricated a multifunctional Cu-MOFs@Keratin DDS for loaded drug and chemodynamic therapy (CDT) against tumor cells. The Cu-MOFs core was prepared using a hydrothermal method, and then loaded with the anticancer drug DOX and wrapped in human hair keratin. The Cu-MOFs@Keratin was well characterized by transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and X-ray photoelectron spectroscopy (XPS). Characterization and pharmacokinetic studies of Cu-MOFs@Keratin were performed and . The keratin shell reduced the cytotoxicity and potential leakage of Cu-MOFs to normal cells, and allowed the drug-loaded nanoparticles to accumulate in the tumor tissues through enhanced permeability and retention effect (EPR). The particles entered the tumor cells endocytosis and disintegrated under the stimulation of intracellular environment, thereby releasing DOX in a controlled manner. In addition, the Cu-MOFs produced hydroxyl radicals (·OH) by consuming presence of high intracellular levels of glutathione (GSH) and HO, which decreased the viability of the tumor cells.

摘要

尽管众多研究已证实金属有机框架(MOF)纳米颗粒作为癌症治疗药物递送系统(DDS)的潜力,但其临床应用仍因生物相容性相对较差而受到限制。我们制备了一种用于负载药物和对肿瘤细胞进行化学动力疗法(CDT)的多功能Cu-MOFs@角蛋白DDS。Cu-MOFs核心采用水热法制备,然后负载抗癌药物阿霉素(DOX)并包裹于人发角蛋白中。通过透射电子显微镜(TEM)、傅里叶变换红外光谱(FTIR)、动态光散射(DLS)和X射线光电子能谱(XPS)对Cu-MOFs@角蛋白进行了充分表征。对Cu-MOFs@角蛋白进行了表征和药代动力学研究。角蛋白外壳降低了Cu-MOFs对正常细胞的细胞毒性和潜在泄漏,并使载药纳米颗粒通过增强渗透滞留效应(EPR)在肿瘤组织中积累。颗粒通过内吞作用进入肿瘤细胞,并在细胞内环境的刺激下分解,从而以可控方式释放DOX。此外,Cu-MOFs通过消耗细胞内高浓度的谷胱甘肽(GSH)和过氧化氢(H₂O₂)产生羟基自由基(·OH),降低了肿瘤细胞的活力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ac8/9936514/cb457e2aa74b/fbioe-11-1125348-g001.jpg

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