School of Chemistry & Chemical Engineering, Inner Mongolia University, 235 West College Road, Hohhot, Inner Mongolia, 010020, PR China.
School of Chemistry & Chemical Engineering, Inner Mongolia University, 235 West College Road, Hohhot, Inner Mongolia, 010020, PR China.
Colloids Surf B Biointerfaces. 2021 Feb;198:111491. doi: 10.1016/j.colsurfb.2020.111491. Epub 2020 Nov 26.
RNA interference technology is a powerful tool with substantially clinical prospects for carcinoma therapy, in which efficiency and specificity of delivery of dsRNA remains a critical issue. Herein, aiming at delivery of dsRNA in efficient and safe way, we constructed targeting delivery platform (CTL-PEG-FA) by grafting curdlan with trilysine through click reaction, then modifying with PEG linked folic acid. The CTL-PEG-FA vector exhibited excellent gene binding capacity to condense siRNA and dramatically reduced cytotoxicity. Increased cell uptake of CTL-PEG-FA/Bcl-2 siRNA was achieved by the synergism of folate mediated endocytosis and charge interaction, and further causing severe HepG2 cells injury through apoptosis mechanism after down-regulation of Bcl-2 protein. In vivo experiments, CTL-PEG-FA/Bcl-2 siRNA complex distinctly accumulated in tumor site and significantly inhibited the growth of tumor, while no obvious toxicity was observed. Therefore, well-performed CTL-PEG-FA with excellent biocompatibility, has the potential to be the candidate of gene therapy for clinical applications.
RNA 干扰技术是一种具有重要临床前景的用于癌症治疗的强大工具，其中双链 RNA 的递呈效率和特异性仍然是一个关键问题。在此，为了以高效和安全的方式递呈双链 RNA，我们通过点击反应将支链淀粉与三赖氨酸接枝，然后用连接有叶酸的聚乙二醇进行修饰，构建了靶向递呈平台（CTL-PEG-FA）。CTL-PEG-FA 载体表现出了优异的基因结合能力，能够将 siRNA 凝聚，并显著降低细胞毒性。通过叶酸介导的内吞作用和电荷相互作用的协同作用，实现了 CTL-PEG-FA/Bcl-2 siRNA 的细胞摄取增加，进而通过下调 Bcl-2 蛋白，导致 HepG2 细胞严重损伤，引发细胞凋亡。在体内实验中，CTL-PEG-FA/Bcl-2 siRNA 复合物明显聚集在肿瘤部位，并显著抑制肿瘤生长，同时未观察到明显的毒性。因此，性能良好的具有优异生物相容性的 CTL-PEG-FA 有望成为临床应用的基因治疗候选物。
