Protamine sulfate/poly(L-aspartic acid) polyionic complexes self-assembled via electrostatic attractions for combined delivery of drug and gene

被引:49
作者
Cheng, Han [1 ]
Li, Yong-Yong [1 ]
Zeng, Xuan [1 ]
Sun, Yun-Xia [1 ]
Zhang, Xian-Zheng [1 ]
Zhuo, Ren-Xi [1 ]
机构
[1] Wuhan Univ, Dept Chem, Minist Educ, Key Lab Biomed Polymers, Wuhan 430072, Peoples R China
基金
中国国家自然科学基金;
关键词
Polyionic complex; Non-viral gene vector; Drug release; Combined delivery; CHITOSAN-DNA NANOPARTICLES; IN-VITRO; NANOGELS; RELEASE;
D O I
10.1016/j.biomaterials.2008.11.002
中图分类号
R318 [生物医学工程];
学科分类号
100103 [病原生物学];
摘要
In this study, a series of self-assembled polyionic complexes (PICs) were prepared via electrostatic attraction between protamine sulfate (PS) and poly(L-aspartic acid) (PASP) or doxorubicin (DOX)-conjugated PASP (DOX-PASP). The size of the PICs measured by Nano-ZS ZEN3600 was around 200-300 nm at different weight ratios of PS/PASR Transmission electron microscopy (TEM) showed that PS/PASP PICs displayed a regular spherical shape and no aggregation was observed. The cytotoxicity study indicated that the PICs did not exhibit apparent cytotoxicity in comparison with that of 25 kDa poly-ethylenimine (PEI). Gel retardation assay indicated that the PICs were able to bind DNA completely when weight ratio of PS/PASP was higher than 2:1. Luciferase assay and green fluorescent protein (GFP) detection were used to confirm that the PICs could be used as efficient non-viral gene vectors and they exhibited comparable transfection efficiency with the one of 25 kDa PEI. Furthermore, confocal laser scanning microscopy as well as suppression activity of DOX-conjugated PICs (DOX-PICs) showed that they could quickly release the loaded DOX into Hela cells, indicating that PICs can be also used as carriers for combined delivery of drug and gene. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1246 / 1253
页数:8
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