摘要
非病毒载体具有质量可控、携带能力高和免疫原性低等优点,但存在转染效率低的致命缺陷,限制了广泛应用。本研究采用计算机模拟设计了新型功能性基团1,3-间苯二甲酰胍(BGG),并通过酰胺键将其修饰于第5代(G5)聚酰胺-胺树枝状大分子表面,得到新型非病毒载体材料G5-BGG。G5-BGG可将基因压缩成荷正电的基因复合物。体外定性和定量转染试验表明,G5-BGG作为基因药物载体可显著提高报告基因在人胃腺癌细胞(SGC-7901)中的转染效率,同时具有良好的生物相容性。G5-BGG负载肿瘤坏死因子相关凋亡诱导配体(pTRAIL)基因时可在细胞水平上诱导SGC-7901细胞凋亡,抑制肿瘤细胞生长,具有良好的抗肿瘤作用。本研究表明G5-BGG在胃癌基因治疗领域具有潜在的应用前景。
Non-viral vectors have the advantages of controllable quality,high carrying capacity and low immunogenicity,but the low transfection efficiency limits their application.In the present study,a new functional group 1,3-dicarbamimidoylisophthal amide(BGG)designed by computer simulation was modified to generation 5(G5)polyamidoamine dendrimer by amido bonds,and the product G5-BGG was used as the carrier for delivery of gene drugs.G5-BGG could condense plasmid DNA into positive complexes.Both qualitative and quantitative transfection experiments in vitro showed that G5-BGG could significantly improve the transfection efficiency of report genes in human gastric adenocarcinoma cells(SGC-7901).Meanwhile,the blank vector G5-BGG possessed good biocompatibility.Besides,tumor necrosis factor-related apoptosis-inducing ligand gene(pTRAIL)loaded gene complex G5-BGG/pTRAIL could induce the apoptosis of SGC-7901 cells and inhibit the growth of SGC-7901 cells.In summary,G5-BGG has the potential application in gastric cancer gene therapy.
作者
宋杰
王董理
张芷依
陆伟跃
刘敏
SONG Jie;WANG Dongli;ZHANG Zhiyi;LU Weiyue;LIU Min(School of Pharmacy,Fudan University,Shanghai 201203)
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2020年第11期1394-1401,共8页
Chinese Journal of Pharmaceuticals
基金
国家自然科学基金面上项目(81973249)
国家自然科学基金重大项目(81690263)
上海市科学技术委员会(20S11905500)
上海市教育委员会科研创新计划项目重大项目(2017-01-07-00-07-E00052)。
