title: Silk-elastinlike protein polymer hydrogels for localized adenoviral gene therapy of head and neck tumors.
abstract: 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.
authors.affiliation: Departments of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
authors.forename: Khaled
authors.initials: K
authors.lastname: Greish
authors.forename: Koji
authors.initials: K
authors.lastname: Araki
authors.forename: Daqing
authors.initials: D
authors.lastname: Li
authors.forename: Bert W
authors.initials: BW
authors.lastname: O'Malley
authors.forename: Ramesh
authors.initials: R
authors.lastname: Dandu
authors.forename: Jordan
authors.initials: J
authors.lastname: Frandsen
authors.forename: Joseph
authors.initials: J
authors.lastname: Cappello
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Ghandehari
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D004337:Drug Carriers; D015316:Genetic Therapy; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000628:therapy*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D008163:Luminescent Measurements; D051379:Mice; D008819:Mice, Nude; D011108:Polymers / Q000737:chemistry*; D011993:Recombinant Fusion Proteins / Q000737:chemistry*; D013937:Thymidine Kinase / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D020100:Hydrogels; D011108:Polymers; D011993:Recombinant Fusion Proteins; C533248:silk-elastinlike protein 47K; D013937:Thymidine Kinase; D001616:beta-Galactosidase