Inhibition of cell proliferation and migration by chondroitin sulfate-g-polyethylenimine-mediated miR-34a delivery.
Inhibition of cell proliferation and migration by chondroitin sulfate-g-polyethylenimine-mediated miR-34a delivery.
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DOI：
10.1016/j.colsurfb.2015.09.054
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发表时间：
2015-12
期刊：
影响因子：
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通讯作者：
Shaojun Liang;Yan‐Xin Duan;Zhen Xing;Haobo Han;Aijun Zhang;Li Li-Li;Yan Yang;Quanshun Li
中科院分区：
文献类型：
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作者：
Shaojun Liang;Yan‐Xin Duan;Zhen Xing;Haobo Han;Aijun Zhang;Li Li-Li;Yan Yang;Quanshun Li
以前列腺肿瘤细胞PC-3为模型，通过Michael加成将硫酸软骨素与PEI25K化学缀合，构建非病毒基因载体CS-PEI，然后将该载体用于miR-34a的递送，从而实现对细胞增殖和迁移的抑制。由质量比为 10 的 CS-PEI 和 miR-34a 制备的纳米颗粒，粒径和 zeta 电位分别为 170.7 nm 和 +42.2 mV。流式细胞术和荧光显微镜显示CS-PEI可以通过CD44介导的内吞作用有效诱导细胞摄取miR-34a。通过CS-PEI介导的miR-34a转染，观察到明显的细胞凋亡，早期凋亡细胞达47.49%，同时检测到caspase-3、-8和-9的激活，以及Bcl-2表达水平的降低。此外，伤口愈合实验表明CS-PEI/miR-34a转染可以抑制细胞迁移。总体而言，CS-PEI 有望用作肿瘤基因治疗中 miR-34a 递送的有前景的肿瘤靶向系统。
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 170.7 nm 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.