Transferrin-functionalized chitosan- graft -poly( l -lysine) dendrons as a high-efficiency gene delivery carrier for nasopharyngeal carcinoma therapy

作者：Tao Liu, Shaohua Chen, Siyi Zhang, Xidong Wu, Peina Wu, Beiping Miao, Xiang Cai · 发表于：Journal of Materials Chemistry B · 年份：2018 · DOI：10.1039/c8tb00489g · 被引用次数：24 · 研究领域：RNA Interference and Gene Delivery、Advanced biosensing and bioanalysis techniques、Virus-based gene therapy research

Transferrin-functionalized chitosan-graft-poly(l-lysine) dendrons (CS-PLLD-Tf) were synthesized in this work and then used to deliver the MMP-9 shRNA plasmid to HNE-1 cells for gene therapy. The obtained CS-PLLD-Tf displayed excellent gene transfection in vitro, verifying the strategy of constructing a high-efficiency gene carrier by conjugating the multiple low generation PLLDs to one molecule of CS to form a copolymer. Particularly, CS-PLLD-Tf showed much higher gene transfection efficiency than PEI-25k and CS-PLLD in the presence of serum, and more than 40% HNE-1 cells were transfected. This result led to an obvious decrease in MMP-9 protein expression and the apoptosis of HNE-1 cells as well as inhibition of the growth and invasion of HNE-1 tumors. The in vivo anti-tumor assay showed that CS-PLLD-Tf delivered the MMP-9 plasmid effectively and the tumor volume decreased more than 77% compared with the PBS control group. Moreover, CS-PLLD-Tf displayed higher bioavailability and good biocompatibility such as lower cytotoxicity, excellent blood compatibility and non-toxicity to organs, suggesting a potential application in gene therapy of tumors.