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聚多巴胺修饰的 ZIF-8 纳米颗粒作为一种药物载体用于联合化疗-光热治疗骨肉瘤。

Polydopamine-modified ZIF-8 nanoparticles as a drug carrier for combined chemo-photothermal osteosarcoma therapy.

机构信息

Institute of Nano-science and Nano-technology, College of Physical Science and Technology, Central China Normal University, Wuhan, Hubei 430079, China.

Institute of Materials Science and Engineering, Henan University of Science and Technology, Luoyang, Henan 471000, China.

出版信息

Colloids Surf B Biointerfaces. 2022 Aug;216:112507. doi: 10.1016/j.colsurfb.2022.112507. Epub 2022 Apr 19.

DOI:10.1016/j.colsurfb.2022.112507
PMID:35523102
Abstract

Single chemotherapy often causes severe adverse effects and chemoresistance which limits therapeutic efficacy. Recently, combination of chemotherapy with photothermal therapy (PTT) have received broad attention for synergistic treatment of osteosarcoma, ultimately resulting in the enhancement of therapeutic efficacy of anticancer drugs. In this study, we have developed a novel drug delivery system based on polydopamine (pDA)-modified ZIF-8 nanoparticles loaded with methotrexate (MTX) (pDA/MTX@ZIF-8 NPs). Herein, pDA modification avoided the explosive release of the drug, and improved the biocompatibility and near-infrared (NIR) light absorbance performance of nanoparticles. The as-prepared pDA/MTX@ZIF-8 NPs could be used as drug targeting delivery system and simultaneously displayed excellent photothermal effects under NIR irradiation. Biology assays in vitro indicated that the pDA/MTX@ZIF-8 NPs were able to efficiently induce MG63 cell apoptosis through reducing mitochondrial membrane potentials (MMPs), and the introduction of photothermal agents enhanced the antitumor effect and decreased the dose of chemotherapeutic drugs. Moreover, the optimized pDA/MTX@ZIF-8 NPs (40 μg/mL) exhibited better photothermal conversion performance and facilitated tumor cells death. These results triumphantly exhibit that the pDA/MTX@ZIF-8 NPs have a synergistic effect of chemo-photothermal therapy (combination index CI = 0.346) and excellent biocompatibility, which has unexceptionable prospects for the therapy of osteosarcoma.

摘要

单一化疗往往会导致严重的不良反应和化疗耐药性,从而限制了治疗效果。最近,化疗与光热疗法(PTT)的联合治疗受到了广泛关注,用于协同治疗骨肉瘤,最终增强了抗癌药物的治疗效果。在这项研究中,我们开发了一种基于聚多巴胺(pDA)修饰的 ZIF-8 纳米粒子负载甲氨蝶呤(MTX)的新型药物传递系统(pDA/MTX@ZIF-8 NPs)。在此,pDA 修饰避免了药物的爆发性释放,并提高了纳米粒子的生物相容性和近红外(NIR)光吸收性能。所制备的 pDA/MTX@ZIF-8 NPs 可用作药物靶向传递系统,并且在近红外照射下同时显示出优异的光热效应。体外生物学研究表明,pDA/MTX@ZIF-8 NPs 通过降低线粒体膜电位(MMPs)能够有效地诱导 MG63 细胞凋亡,并且引入光热剂增强了抗肿瘤作用并降低了化疗药物的剂量。此外,优化的 pDA/MTX@ZIF-8 NPs(40μg/mL)表现出更好的光热转换性能,并促进了肿瘤细胞死亡。这些结果成功地表明,pDA/MTX@ZIF-8 NPs 具有化学-光热治疗的协同作用(组合指数 CI = 0.346)和优异的生物相容性,为骨肉瘤的治疗提供了无可挑剔的前景。

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