Silk-elastinlike protein polymer hydrogels for localized adenoviral gene therapy of head and neck tumors.
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.
Greish
Khaled
K
Departments of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Araki
Koji
K
Li
Daqing
D
O'Malley
Bert W
BW
Dandu
Ramesh
R
Frandsen
Jordan
J
Cappello
Joseph
J
Ghandehari
Hamidreza
H
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
D004337:Drug Carriers; D020100:Hydrogels; D011108:Polymers; D011993:Recombinant Fusion Proteins; C533248:silk-elastinlike protein 47K; D013937:Thymidine Kinase; D001616:beta-Galactosidase