Preparation of reduction-triggered degradable microcapsules for intracellular delivery of anti-cancer drug and gene
Preparation of reduction-triggered degradable microcapsules for intracellular delivery of anti-cancer drug and gene
复制标题
还原触发可降解微胶囊的制备用于细胞内递送抗癌药物和基因
DOI：
10.1016/j.polymer.2013.11.035
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发表时间：
2014-01-14
期刊：
影响因子：
4.6
通讯作者：
Yang, Xinlin
中科院分区：
文献类型：
--
作者：
Feng, Fuli;Li, Rongrong;Yang, Xinlin
采用蒸馏-沉淀聚合法制备了可还原降解的聚(甲基丙烯酸-N，N-双(丙烯酰基)半胺)/聚乙烯亚胺(P(MAA-co-BAc)/PEI)微胶囊，用于抗癌药物和基因的传递。N，N-双(丙烯酰基)半胺(BAC)作为一种含有二硫键的交联剂，可以被还原型谷胱甘肽(GSH)和二硫苏糖醇(DTT)引发，从而使功能微囊具有还原引发的药物释放。用透射电子显微镜、傅里叶变换红外光谱、激光粒度仪和元素分析对P(MAA-co-BAC)/PEI微胶囊进行了表征。通过UV-Vis光谱分析研究了微胶囊的降解行为。以盐酸阿霉素(DOX)为模型药物分子，P(MAA-co-BAC)/PEI微囊的药物控释行为强烈依赖于GSH的存在和pH值。用绿色荧光蛋白(GFP)编码的质粒DNA(PDNA)对Hela细胞进行体外基因转染率的检测，并用共聚焦荧光显微镜检测其转染率。用WST-1比色法测定了(P(MAA-co-BAC)/PEI)微囊在负载DOX前后的细胞毒性。P(MAA-co-BAC)/PEI微囊为药物和基因传递提供了潜在的新型载体，在抗癌药物和基因联合治疗中具有广阔的应用前景。(C)2013爱思唯尔有限公司。保留所有权利。
The reduction-triggered degradable poly(methacrylic acid-co-N,N-bis(acryloyl)cystamine)/polyethyleneimine (P(MAA-co-BAC)/PEI) microcapsules were prepared by distillation-precipitation polymerization for delivery of anti-cancer drug and gene. N,N-bis(acryloyl)cystamine (BAC) as a crosslinker containing a disulfide bond can be triggered by reductive agents, such as glutathione (GSH) and dithiothreitol (DTT), to endow the functional microcapsules with reduction-triggered drug release. The P(MAA-co-BAC)/PEI microcapsules were characterized by transmission electron microscopy (TEM), Fourier-transform infrared spectra (FT-IR), laser particle size analyzer and elemental analysis. The degradable behavior of microcapsules was investigated by analysis of UV-vis spectroscopy. The controlled drug release behavior for P(MAA-co-BAC)/PEI microcapsules was strongly dependent on the absence/presence of GSH and the pH values with doxorubicin hydrochloride (DOX) as a model drug molecule. The in vitro gene transfection ability was evaluated by Hela cells with the transfection of plasmid DNA (pDNA) encoded with green fluorescent protein (GFP) and the transfection efficiency was determined by confocal fluorescence microscopy. Furthermore, the cytotoxicities of (P(MAA-co-BAC)/PEI) microcapsules before and after loading of DOX were assessed via WST-1 assay. The P(MAA-co-BAC)/PEI microcapsules provide the potential novel vectors for delivery of drugs and genes, promising for future applications in anticancer drug and gene combined therapy. (C) 2013 Elsevier Ltd. All rights reserved.