School of Chemistry and Chemical Engineering, Qinghai University for Nationalities, Xining, Qinghai 810007, P. R. China.
Key Laboratory of National Ethnic Affairs Commission of Resource Chemistry and Ecological Environment Protection on Qinghai-Tibet Plateau, Xining, Qinghai 810007, P. R. China.
J Mater Chem B. 2024 Mar 13;12(11):2843-2854. doi: 10.1039/d3tb02849f.
Cationic copolymers are widely used in gene delivery as a non-viral gene vector, but their applications are limited by low transfection efficiency and high cytotoxicity. In order to enhance the transfection efficiency of copolymer micelles to endothelial cells (HUVECs) and reduce their cytotoxicity, this study synthesized an amphipathic multi-targeted copolymer micelle delivery system PCLMD-PPEGMA-NLS-TAT-REDV (TCMs). Gel test results showed that TCMs showed good pZNF580 binding ability and could effectively load the pZNF580 plasmid. The CCK-8 results show that when the concentration of TCMs is greater than 60 μg mL, it will affect cell viability and have low cytotoxicity. We found that the multi-targeted copolymer micelles can be effectively taken up by HUVECs . The transfection efficiency of TCMs@pZNF580 (w/w = 3) to HUVECs was comparable to that of the positive control group lip2000@pZNF580, and WB also showed the same trend. In addition, the TCMs@pZNF580 complex also significantly enhanced the proliferation and migration of HUVECs. The experimental results on blood vessel formation showed that TCMs@pZNF580 accelerated the vascularization of HUVECs. This experiment provided a new technology platform for targeted gene therapy, especially for endothelialization and vascularization. The research results have important reference value for the treatment of cardiovascular diseases.
阳离子共聚物作为一种非病毒基因载体，广泛应用于基因传递，但由于转染效率低和细胞毒性高，其应用受到限制。为了提高共聚物胶束对内皮细胞（HUVEC）的转染效率并降低其细胞毒性，本研究合成了一种两亲性多靶向共聚物胶束递药系统 PCLMD-PPEGMA-NLS-TAT-REDV（TCMs）。凝胶试验结果表明 TCMs 具有良好的 pZNF580 结合能力，并能有效负载 pZNF580 质粒。CCK-8 结果表明，当 TCMs 的浓度大于 60μg mL 时，会影响细胞活力，具有低细胞毒性。我们发现多靶向共聚物胶束可以被 HUVECs 有效摄取。TCMs@pZNF580（w/w=3）对 HUVECs 的转染效率可与阳性对照组 lip2000@pZNF580 相媲美，WB 也表现出相同的趋势。此外，TCMs@pZNF580 复合物还显著增强了 HUVECs 的增殖和迁移。血管生成实验结果表明，TCMs@pZNF580 加速了 HUVECs 的血管生成。该实验为靶向基因治疗提供了一个新技术平台，特别是在内皮化和血管化方面。研究结果对心血管疾病的治疗具有重要的参考价值。
