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用于去唾液酸糖蛋白受体靶向抗癌药物递送的乳糖胺化介孔二氧化硅纳米颗粒

Lactosaminated mesoporous silica nanoparticles for asialoglycoprotein receptor targeted anticancer drug delivery.

作者信息

Quan Guilan, Pan Xin, Wang Zhouhua, Wu Qiaoli, Li Ge, Dian Linghui, Chen Bao, Wu Chuanbin

机构信息

School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, People's Republic of China.

Guangzhou Neworld Pharmaceutical Ltd. Co., Guangzhou, 510006, People's Republic of China.

出版信息

J Nanobiotechnology. 2015 Feb 3;13:7. doi: 10.1186/s12951-015-0068-6.

DOI:10.1186/s12951-015-0068-6
PMID:25643602
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4333889/
Abstract

BACKGROUND: Mesoporous silica nanoparticles (MSNs) have several attractive properties as a drug delivery system, such as ordered porous structure, large surface area, controllable particle size as well as interior and exterior dual-functional surfaces. The purpose of this study was to develop novel lactosaminated mesoporous silica nanoparticles (Lac-MSNs) for asialoglycoprotein receptor (ASGPR) targeted anticancer drug delivery. RESULTS: Lac-MSNs with an average diameter of approximately 100 nm were prepared by conjugation of lactose with 3-aminopropyl triethoxysilane modified MSNs. Characterization of Lac-MSNs indicated a huge Brunauer-Emmett-Teller (BET) surface area (1012 m(2)/g), highly ordered 2D hexagonal symmetry, an unique mesoporous structure with average pore size of 3.7 nm. The confocal microscopy and flow cytometric analysis illustrated Lac-MSNs were effectively endocytosed by ASGPR-positive hepatoma cell lines, HepG2 and SMMC7721. In contrast, non-selective endocytosis of Lac-MSNs was found in ASGPR-negative NIH 3T3 cells. The cellular uptake study showed the internalization process was energy-consuming and predominated by clathrin-mediated pathway. Model drug docetaxel (DTX) was loaded in the mesopores of Lac-MSNs by wetness impregnation method. In vitro cytotoxicity assay showed that DTX transported by Lac-MSNs effectively inhibited the growth of HepG2 and SMMC7721 cells in a time- and concentration- dependent manner. CONCLUSIONS: These results demonstrated that Lac-MSNs could be a promising inorganic carrier system for targeted intracellular anti-cancer drug delivery.

摘要

背景：介孔二氧化硅纳米颗粒（MSNs）作为一种药物递送系统具有多种吸引人的特性，如有序的多孔结构、大表面积、可控的粒径以及内外双功能表面。本研究的目的是开发新型乳糖胺化介孔二氧化硅纳米颗粒（Lac-MSNs）用于去唾液酸糖蛋白受体（ASGPR）靶向抗癌药物递送。 结果：通过将乳糖与3-氨丙基三乙氧基硅烷修饰的MSNs偶联制备了平均直径约为100 nm的Lac-MSNs。Lac-MSNs的表征显示出巨大的布鲁诺尔-埃米特-泰勒（BET）表面积（1012 m²/g）、高度有序的二维六方对称性、平均孔径为3.7 nm的独特介孔结构。共聚焦显微镜和流式细胞术分析表明，Lac-MSNs被ASGPR阳性肝癌细胞系HepG2和SMMC7721有效内吞。相比之下，在ASGPR阴性的NIH 3T3细胞中发现Lac-MSNs的非选择性内吞。细胞摄取研究表明内化过程是耗能的，且以网格蛋白介导的途径为主。通过湿浸渍法将模型药物多西他赛（DTX）负载到Lac-MSNs的介孔中。体外细胞毒性试验表明，Lac-MSNs转运的DTX以时间和浓度依赖性方式有效抑制HepG2和SMMC7721细胞的生长。 结论：这些结果表明，Lac-MSNs可能是一种有前途的无机载体系统，用于靶向细胞内抗癌药物递送。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/5aa3b875cc8d/12951_2015_68_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/582cc4d3866e/12951_2015_68_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/7b998b84985a/12951_2015_68_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/4c8be0b953f7/12951_2015_68_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/ceba2956f6a0/12951_2015_68_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/75a02a66a99c/12951_2015_68_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/8f6a286a8100/12951_2015_68_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/564cd1d30b30/12951_2015_68_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/5aa3b875cc8d/12951_2015_68_Fig11_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/582cc4d3866e/12951_2015_68_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/1490bc282d1e/12951_2015_68_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/0ee2e02c403f/12951_2015_68_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/92c556f92324/12951_2015_68_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/7b998b84985a/12951_2015_68_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/4c8be0b953f7/12951_2015_68_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/ceba2956f6a0/12951_2015_68_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/75a02a66a99c/12951_2015_68_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/8f6a286a8100/12951_2015_68_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/564cd1d30b30/12951_2015_68_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27dc/4333889/5aa3b875cc8d/12951_2015_68_Fig11_HTML.jpg

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