Silk-Elastinlike Protein Polymer Hydrogels for Localized Adenoviral Gene Therapy of Head and Neck Tumors
Silk-Elastinlike Protein Polymer Hydrogels for Localized Adenoviral Gene Therapy of Head and Neck Tumors
复制标题
DOI：
10.1021/bm900356j
复制
发表时间：
2009-08-01
影响因子：
6.2
通讯作者：
Ghandehari, Hamidreza
中科院分区：
文献类型：
--
作者：
Greish, Khaled;Araki, Koji;Ghandehari, Hamidreza
载体传播、瞬时基因表达和快速清除是人类基因治疗成功的主要障碍。在这项研究中，我们研究了丝弹性蛋白样蛋白聚合物（SELP）水凝胶对头颈癌模型中腺病毒基因治疗的生物分布和抗癌功效的影响。在患有头颈癌的 (nu/nu) 小鼠中评估了携带 β-半乳糖苷酶 (Ad-LacZ) 和荧光素酶 (Ad-Luc) 报告基因的腺病毒的转录活性，作为聚合物浓度的函数。还评估了编码腺病毒（Ad-Tk）和更昔洛韦（GSV）组合的胸苷激酶的抗肿瘤功效。 SELP (4 wt%) 基质局部病毒释放。与单独的病毒相比，最大限度地减少了向肝脏的传播，并将报告基因表达水平提高了 4-8 倍。与单独使用病毒相比，SELP-Ad-Tk 与 GSV 显着减小了肿瘤体积。 SELP 提供了一种在时间和空间上控制病毒基因向头颈部肿瘤传递的方法。
Vector dissemination, transient gene expression, and rapid clearance are major obstacles to successful human gene therapy. In this study, we investigated the effect of silk-elastinlike protein polymer (SELP) hydrogels on biodistribution and anticancer efficacy of adenoviral gene therapy in a head and neck cancer model. Transcriptional activities of adenovirus carrying beta-galactosidase (Ad-LacZ) and luciferase (Ad-Luc) reporter genes were evaluated in (nu/nu) mice with head and neck cancer as a function of polymer concentration. Antitumor efficacy of thymidine kinase encoding adenovirus (Ad-Tk) and ganciclovir (GSV) combination was also evaluated. SELP (4 wt%) matrices localized viral release. minimized dissemination to liver, and enhanced reporter gene expression levels by 4-8-fold compared to virus alone. SELP-Ad-Tk with GSV reduced tumor volume significantly compared to the virus alone. SELPs provide a means for temporal and spatial control of viral gene delivery to head and neck tumors.