Trilayer micelles for combination delivery of rapamycin and siRNA targeting Y-box binding protein-1 (siYB-1).
Trilayer micelles for combination delivery of rapamycin and siRNA targeting Y-box binding protein-1 (siYB-1).
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DOI：
10.1016/j.biomaterials.2013.05.010
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发表时间：
2013-09
期刊：
影响因子：
14
通讯作者：
Xiong, May P.
中科院分区：
文献类型：
--
作者：
Zeng, San;Xiong, May P.
合成了一种基于三嵌段聚合物聚乙二醇-b-聚{N-[N-（2-氨基乙基）-2-氨基乙基]阿斯巴酰胺}-b-聚（ε-己内酯）（PEG-b-PAsp(DET)-b- pcl）自缔合的三层（三层）聚合物胶束体系，并研究了用于联合递送雷帕霉素（RAP）和靶向Y-box结合蛋白-1 （siYB-1）的siRNA。三层胶束由(a)亲水聚乙二醇（PEG）块构成外层以改善药代动力学，(b)由阳离子聚{2-[（2-氨基乙基）氨基]乙基阿斯巴冬酰胺}（PAsp(DET)）段组成的中间隔室与siYB-1相互作用，(c)内疏水聚（ε-己内酯）（PCL）隔室包封RAP。该系统的一个主要优点是生物相容性，因为PEG和PCL都通过了FDA的批准，而PAsp（DET）是一种无毒的pH响应阳离子聚（氨基酸）基聚合物。在这项研究中，已经证明PCL可以以高负载效率封装RAP， PAsp（DET）可以成功地与siRNA相互作用，以有效的转染/敲低，而细胞毒性可以忽略不计。RAP/ siYB-1胶束在细胞培养和人前列腺癌PC3异种移植裸鼠模型中显示了增强的治疗效果。在此，我们证明了三层胶束是一种很有前途的方法，可以改善siRNA/药物联合治疗的同时递送。
A three layer (trilayer) polymeric micelle system based on the self-association of the triblock polymer poly(ethylene glycol)-b-poly{N-[N-(2-aminoethyl)-2-aminoethyl] aspartamide}-b-poly(ε-caprolactone) (PEG-b-PAsp(DET)-b-PCL) has been synthesized and investigated for combination delivery of rapamycin (RAP) and siRNA targeting Y-box binding protein-1 (siYB-1). The trilayer micelle is composed of (a) a hydrophilic poly(ethylene glycol) (PEG) block constituting the outer layer to improve pharmacokinetics, (b) an intermediate compartment composed of the cationic poly{2-[(2-aminoethyl)amino] ethyl aspartamide} (PAsp(DET)) segment for interacting with siYB-1, and (c) an inner hydrophobic poly(ε-caprolactone) (PCL) compartment for encapsulation of RAP. A major advantage of this system is biocompatibility since PEG and PCL are both approved by the FDA, and PAsp(DET) is a non-toxic pH responsive cationic poly(amino acid)-based polymer. In this study, it has been shown that PCL can encapsulate RAP with high loading efficiencies, and PAsp(DET) can successfully interact with siRNA for efficient transfection/knockdown with negligible cytotoxicity. The enhanced therapeutic efficacy of RAP/ siYB-1 micelles was demonstrated in cell cultures and in a PC3 xenograft nude mouse model of human prostate cancer. Herein, we demonstrate that trilayer micelles are a promising approach to improve the simultaneous delivery of combination siRNA/drug therapies.
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DOI：
10.1158/1078-0432.ccr-09-1249
发表时间：
2009-12-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Gulhati P;Cai Q;Li J;Liu J;Rychahou PG;Qiu S;Lee EY;Silva SR;Bowen KA;Gao T;Evers BM
通讯作者：
Evers BM
影响因子：
3.7
作者：
Law, Jennifer H.;Li, Yvonne;Dunn, Sandra E.
通讯作者：
Dunn, Sandra E.
影响因子：
10.8
作者：
Gary, Dana J.;Puri, Nitin;Won, You-Yeon
通讯作者：
Won, You-Yeon
影响因子：
10.8
作者：
Kakizawa, Y;Furukawa, S;Kataoka, K
通讯作者：
Kataoka, K
DOI：
10.1016/j.bbrc.2010.06.104
发表时间：
2010-07-30
影响因子：
3.1
作者：
Lovett, David H.;Cheng, Sunfa;Cape, Leslie;Pollock, Allan S.;Mertens, Peter R.
通讯作者：
Mertens, Peter R.