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Transferrin-functionalized chitosan-graft-poly(l-lysine) dendrons as a high-efficiency gene delivery carrier for nasopharyngeal carcinoma therapy†
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2018-06-09 00:00:00 , DOI: 10.1039/c8tb00489g Tao Liu 1, 2, 3, 4, 5 , Shaohua Chen 1, 2, 3, 4, 5 , Siyi Zhang 1, 2, 3, 4, 5 , Xidong Wu 5, 6, 7, 8 , Peina Wu 1, 2, 3, 4, 5 , Beiping Miao 5, 9, 10, 11, 12 , Xiang Cai 5, 13, 14, 15
Journal of Materials Chemistry B ( IF 6.1 ) Pub Date : 2018-06-09 00:00:00 , DOI: 10.1039/c8tb00489g Tao Liu 1, 2, 3, 4, 5 , Shaohua Chen 1, 2, 3, 4, 5 , Siyi Zhang 1, 2, 3, 4, 5 , Xidong Wu 5, 6, 7, 8 , Peina Wu 1, 2, 3, 4, 5 , Beiping Miao 5, 9, 10, 11, 12 , Xiang Cai 5, 13, 14, 15
Affiliation
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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.
中文翻译：
转铁蛋白官能化的壳聚糖接枝聚l赖氨酸树突状细胞作为鼻咽癌治疗的高效基因传递载体†
在这项工作中合成了转铁蛋白官能化的壳聚糖-嫁接-聚（L-赖氨酸）树突（CS–PLLD–Tf），然后用于将MMP-9 shRNA质粒递送至HNE-1细胞进行基因治疗。所获得的CS–PLLD–Tf在体外表现出优异的基因转染，通过将多个低代PLLD与CS分子结合形成共聚物来验证构建高效基因载体的策略。特别是在存在血清的情况下，CS–PLLD–Tf的基因转染效率要高于PEI-25k和CS–PLLD，并且转染了40％以上的HNE-1细胞。该结果导致MMP-9蛋白表达和HNE-1细胞的凋亡显着降低以及对HNE-1肿瘤的生长和侵袭的抑制。这体内抗肿瘤试验显示CS–PLLD–Tf有效递送MMP-9质粒，与PBS对照组相比，肿瘤体积减少了77％以上。此外，CS–PLLD–Tf表现出更高的生物利用度和良好的生物相容性，例如较低的细胞毒性，出色的血液相容性和对器官的无毒性，表明其在肿瘤基因治疗中的潜在应用。
更新日期：2018-06-09
中文翻译：
转铁蛋白官能化的壳聚糖接枝聚l赖氨酸树突状细胞作为鼻咽癌治疗的高效基因传递载体†
在这项工作中合成了转铁蛋白官能化的壳聚糖-嫁接-聚（L-赖氨酸）树突（CS–PLLD–Tf），然后用于将MMP-9 shRNA质粒递送至HNE-1细胞进行基因治疗。所获得的CS–PLLD–Tf在体外表现出优异的基因转染，通过将多个低代PLLD与CS分子结合形成共聚物来验证构建高效基因载体的策略。特别是在存在血清的情况下，CS–PLLD–Tf的基因转染效率要高于PEI-25k和CS–PLLD，并且转染了40％以上的HNE-1细胞。该结果导致MMP-9蛋白表达和HNE-1细胞的凋亡显着降低以及对HNE-1肿瘤的生长和侵袭的抑制。这体内抗肿瘤试验显示CS–PLLD–Tf有效递送MMP-9质粒，与PBS对照组相比，肿瘤体积减少了77％以上。此外，CS–PLLD–Tf表现出更高的生物利用度和良好的生物相容性，例如较低的细胞毒性，出色的血液相容性和对器官的无毒性，表明其在肿瘤基因治疗中的潜在应用。
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