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介孔铁羧酸金属有机骨架通过双模板法合成作为肿瘤内药物递送的纳米载体平台。

Mesoporous iron-carboxylate metal-organic frameworks synthesized by the double-template method as a nanocarrier platform for intratumoral drug delivery.

机构信息

College of Chemical Engineering, Sichuan University, Chengdu 610065, China.

出版信息

Biomater Sci. 2017 May 2;5(5):1032-1040. doi: 10.1039/c7bm00028f.

DOI:10.1039/c7bm00028f
PMID:28358402
Abstract

Metal-organic frameworks as a powerful platform for drug delivery have attracted significant attention in recent years. In this study, mesoporous iron-metal-organic framework nanoparticles (mesoMOFs) were synthesized via the double-template method. Cetyltrimethylammonium bromide (CTAB) and citric acid (CA) were chosen as the double-template agent. The mesoMOFs were characterized by EDX, elemental analysis, TG, BET, SEM, TEM, and DLS. The anticancer drug doxorubicin hydrochloride (DOX) was encapsulated in the mesoMOFs, and the DOX loading content was up to 55 wt%. The mesoMOFs are non-toxic to both 4T1 breast cancer cells and 3T3 fibroblasts. The DOX-loaded mesoMOFs exhibit a better anti-tumor effect than free doxorubicin in vitro. The in vivo anticancer activities of the DOX-loaded mesoMOFs were investigated in 4T1 breast cancer-bearing mice. The intratumoral injection of DOX-loaded mesoMOFs revealed that the mesoMOFs could significantly reduce the systemic toxicity of DOX, sustainably release DOX, and maintain an effective DOX concentration for chemotherapy. The DOX-loaded mesoMOFs exhibit excellent therapeutic efficacy and low side effects in local chemotherapy.

摘要

金属有机骨架作为一种强大的药物输送平台,近年来引起了广泛关注。本研究通过双模板法合成了介孔铁金属有机骨架纳米粒子(mesoMOFs)。选择十六烷基三甲基溴化铵(CTAB)和柠檬酸(CA)作为双模板剂。通过 EDX、元素分析、TG、BET、SEM、TEM 和 DLS 对 mesoMOFs 进行了表征。盐酸阿霉素(DOX)被包裹在介孔 MOFs 中,DOX 的负载量高达 55wt%。介孔 MOFs 对 4T1 乳腺癌细胞和 3T3 成纤维细胞均无毒性。载 DOX 的介孔 MOFs 在体外表现出比游离阿霉素更好的抗肿瘤效果。在荷 4T1 乳腺癌小鼠中研究了载 DOX 的介孔 MOFs 的体内抗癌活性。DOX 载介孔 MOFs 的瘤内注射表明,介孔 MOFs 可以显著降低 DOX 的全身毒性,持续释放 DOX,并维持化疗的有效 DOX 浓度。载 DOX 的介孔 MOFs 在局部化疗中表现出优异的治疗效果和低副作用。

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