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用于乳腺癌细胞中抗癌药物递送的UiO-66和ZIF-8金属有机框架纳米载体的研发

Development of UiO-66 and ZIF-8 MOF Nanocarriers for Anticancer Drug Delivery in Breast Cancer Cells.

作者信息

Priyadarshini Anulipsa, Senapati Deepak, Das Niharika, Gupta Sonali, Swain Jaykishon, Samal Debadutta, Barick K C, Sahu Rojalin

机构信息

Future Materials Laboratory, Department of chemistry, School of Applied Sciences, Kalinga Institute of Industrial Technology (deemed to be university), Bhubaneswar, Odisha, 751024, India.

Chemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai, 400085, India.

出版信息

Chem Asian J. 2025 Sep 16:e00672. doi: 10.1002/asia.202500672.

Abstract

Metal-organic frameworks (MOFs), characterized by their extensive surface area, biocompatibility, and pH-sensitive degradation have emerged as promising candidates for drug delivery systems (DDSs). This study focused on the development of zinc based zeolitic imidazolate framework (ZIF8) and zirconium-based framework (UiO-66) MOFs as effective nanocarriers for delivery of broad-spectrum chemotherapeutic drug, doxorubicin hydrochloride (DOX), aiming to mitigate adverse side effects in breast cancer treatment. The nanocarriers, ZIF-8 and UiO-66 achieved a maximum drug loading efficiency of about between 79% and 75% at a drug-to-particle ratio of 1:10, and exhibited their pH-responsive release, which is essential for cancer therapy. The in vitro therapeutic efficacy of developed DDSs was explored on breast cancer (MCF-7 and MDA-MB-231) cell lines as well lung normal cells (WI26VA4). From confocal microscopic studies, it has been observed that a substantial amount of DOX is internalized into the cancer cells in a time-dependent manner. It is noteworthy to mention that both the developed drug formulations (DOX@UiO-66 and DOX@ZIF-8) showed dose-dependent toxicity towards cancer cell lines. Moreover, the cell viability studies performed with pure ZIF-8 and UiO-66 MOFs against normal as well as cancer cells demonstrated their biocompatibility nature even at a high concentration of 50 µg/mL. These findings underscore the potential of ZIF-8 and UiO-66 MOFs as effective and biocompatible platforms for drug delivery in breast cancer therapy.

摘要

金属有机框架材料(MOFs),以其大比表面积、生物相容性和pH敏感降解特性,已成为药物递送系统(DDSs)的有前景候选材料。本研究聚焦于开发锌基沸石咪唑酯骨架材料(ZIF8)和锆基骨架材料(UiO - 66)作为广谱化疗药物盐酸阿霉素(DOX)递送的有效纳米载体,旨在减轻乳腺癌治疗中的不良副作用。纳米载体ZIF - 8和UiO - 66在药物与颗粒比例为1:10时实现了约79%至75%的最大载药效率,并表现出pH响应释放,这对癌症治疗至关重要。在乳腺癌(MCF - 7和MDA - MB - 231)细胞系以及肺正常细胞(WI26VA4)上探索了所开发DDSs的体外治疗效果。通过共聚焦显微镜研究观察到,大量DOX以时间依赖性方式内化到癌细胞中。值得注意的是,所开发的两种药物制剂(DOX@UiO - 66和DOX@ZIF - 8)对癌细胞系均表现出剂量依赖性毒性。此外,用纯ZIF - 8和UiO - 66 MOFs对正常细胞和癌细胞进行的细胞活力研究表明,即使在50 µg/mL的高浓度下它们也具有生物相容性。这些发现强调了ZIF - 8和UiO - 66 MOFs作为乳腺癌治疗中有效且生物相容的药物递送平台的潜力。

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