Silk-Elastinlike Protein Polymer Hydrogels for Localized Adenoviral Gene Therapy of Head and Neck Tumors

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• 作者：Khaled Greish ; Koji Araki ; Daqing Li ; Bert W. O’ ; Malley ; Jr. ; Ramesh Dandu ; Jordan Frandsen ; Joseph Cappello ; Hamidreza Ghandehari
• 刊名：Biomacromolecules
• 出版年：2009
• 出版时间：August 10, 2009
• 年：2009
• 卷：10
• 期：8
• 页码：2183-2188
• 全文大小：413K
• 年卷期：v.10,no.8(August 10, 2009)
• ISSN：1526-4602

文摘

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 β-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.