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叶酸和脱氧胆酸衍生物修饰的FeO纳米颗粒用于高效pH依赖型药物释放及对肝癌细胞的多靶点作用

Folic acid and deoxycholic acid derivative modified FeO nanoparticles for efficient pH-dependent drug release and multi-targeting against liver cancer cells.

作者信息

Wang Xiaoyu, Ma Qing, Wen Chaochao, Gong Tao, Li Jing, Liang Wenting, Li Meining, Wang Yuyao, Guo Rui

机构信息

Department of Biochemistry and Molecular Biology, Shanxi Medical University Taiyuan 030001 China

Institute of Environmental Science, Department of Chemistry, Shanxi University Taiyuan 030006 China

出版信息

RSC Adv. 2021 Dec 14;11(63):39804-39812. doi: 10.1039/d1ra05874f. eCollection 2021 Dec 13.

DOI:10.1039/d1ra05874f
PMID:35494148
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9044570/
Abstract

The novel nano-drug carrier (FDCA-FA-MNPs) was constructed by grafting formyl deoxycholic acid (FDCA) and folic acid (FA) on the surface of FeO magnetic nanoparticles (MNPs), possessing the advantages of superparamagnetism, good stability, low cytotoxicity and good blood compatibility. The hydrophobic anti-cancer drug doxorubicin hydrochloride (DOX) was successfully loaded onto FDCA-FA-MNPs through supramolecular interactions (hydrogen bond between FDCA and drug and hydrophobic interaction and π-π stacking between drug and drug). The drug loading amount and drug loading capacity were 509.1 mg g and 33.73 wt%, respectively. In addition, drug release had a pH responsive and controllable release performance, the release rate at pH 5.3 (45.6%) was four times that at pH 7.4 (11.5%), and the tumor microenvironment was favorable for drug release. More importantly, the novel nano-drug carrier combined the hepatocellular targeting of FDCA, the cancer cell targeting of FA, and the magnetic targeting of FeO, showing excellent cancer-killing efficiency (78%) . Therefore, the nano-drug carrier synthesized in this paper has potential practical application value in the targeted therapy of liver cancer.

摘要

通过将甲酰脱氧胆酸(FDCA)和叶酸(FA)接枝到FeO磁性纳米颗粒(MNPs)表面构建了新型纳米药物载体(FDCA-FA-MNPs),其具有超顺磁性、良好的稳定性、低细胞毒性和良好的血液相容性等优点。疏水性抗癌药物盐酸阿霉素(DOX)通过超分子相互作用(FDCA与药物之间的氢键以及药物与药物之间的疏水相互作用和π-π堆积)成功负载到FDCA-FA-MNPs上。载药量和载药率分别为509.1 mg g和33.73 wt%。此外,药物释放具有pH响应性和可控释放性能,pH 5.3时的释放率(45.6%)是pH 7.4时(11.5%)的四倍,肿瘤微环境有利于药物释放。更重要的是,新型纳米药物载体结合了FDCA的肝细胞靶向性、FA的癌细胞靶向性和FeO的磁靶向性,显示出优异的杀癌效率(78%)。因此,本文合成的纳米药物载体在肝癌的靶向治疗中具有潜在的实际应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6123/9044570/1fc31a939b82/d1ra05874f-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6123/9044570/585d566684a5/d1ra05874f-s1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6123/9044570/39321a8028f3/d1ra05874f-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6123/9044570/1fc31a939b82/d1ra05874f-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6123/9044570/585d566684a5/d1ra05874f-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6123/9044570/790491d18dce/d1ra05874f-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6123/9044570/1e77a160bd12/d1ra05874f-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6123/9044570/7f519cdef624/d1ra05874f-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6123/9044570/1919cd8abb6c/d1ra05874f-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6123/9044570/65b2f207c979/d1ra05874f-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6123/9044570/9af5bf498e7c/d1ra05874f-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6123/9044570/57ee847cc68b/d1ra05874f-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6123/9044570/39321a8028f3/d1ra05874f-f8.jpg
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