Inhibition of cell proliferation and migration by chondroitin sulfate-g-polyethylenimine-mediated miR-34a delivery

被引:16
作者
Liang, Shaojun [1 ]
Duan, Yan [1 ]
Xing, Zhen [1 ]
Han, Haobo [1 ]
Zhang, Aijun [1 ]
Li, Li [2 ]
Yang, Yan [1 ]
Li, Quanshun [1 ]
机构
[1] Jilin Univ, Sch Life Sci, Minist Educ, Key Lab Mol Enzymol & Engn, Changchun 130012, Peoples R China
[2] Changchun Women & Childrens Hlth, Dept Clin Lib, Changchun 130021, Peoples R China
关键词
Chondroitin sulfate; Polyethylenimine; CD44; MiR-34a; Apoptosis; Cell migration; CANCER STEM-CELLS; GENE DELIVERY; SYSTEMIC DELIVERY; BREAST-CANCER; THERAPY; NANOPARTICLES; CD44; NANOCARRIERS; HYALURONAN; COPOLYMERS;
D O I
10.1016/j.colsurfb.2015.09.054
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Chondroitin sulfate was chemically conjugated to PEI25K through Michael addition to construct a non-viral gene carrier CS-PEI, and then the carrier was employed in miR-34a delivery to achieve the inhibition of cell proliferation and migration, using prostate tumor cell PC-3 as a model. The nanoparticle from CS-PEI and miR-34a at a mass ratio of 10 was prepared with particle size and zeta potential of 170.7nm and +42.2 mV, respectively. Flow cytometry and fluorescence microscopy revealed that CS-PEI could efficiently induce the cellular uptake of miR-34a in a CD44-mediated endocytosis manner. Through CS-PEI-mediated miR-34a transfection, obvious cell apoptosis was observed with early apoptotic cells of 47.49%, and meanwhile the activation of caspase-3, -8 and -9, and decreased expression level of Bcl-2 were detected. Moreover, wound healing assay showed that CS-PEI/miR-34a transfection could inhibit the cell migration. Overall, CS-PEI is potentially employed as a promising tumor-targeting system for miR-34a delivery in tumor gene therapy. (C) 2015 Elsevier B.V. All rights reserved.
引用
收藏
页码:577 / 584
页数:8
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