Jung, Se-Hui Choi, Joung-Woo Yun, Chae-Ok Yhee, Ji Young Price, Robert Kim, Sun Hwa Kwon, Ick Chan Ghandehari, Hamidreza 2024-01-20T10:00:55Z 2024-01-20T10:00:55Z 2021-09-05 2014-05 1099-498X https://pubs.kist.re.kr/handle/201004/126835 Background Oncolytic adenovirus (Ad)-mediated gene therapy is a promising approach for suppression of primary tumors. Therapeutic efficacy of Ad-mediated gene therapy has been limited by immunogenicity, rapid dissemination of viral progenies into systemic circulation and short duration of biological activity. Polymeric sustained local delivery can overcome many of these challenges to produce a viable therapy with improved outcomes. Methods Silk-elastinlike protein polymer (SELP) hydrogels were used for matrix-mediated delivery of oncolytic Ad, containing short hairpin RNA (shRNA) targeted to C-Met (sh-C-Met), to solid tumors in a nude mouse model of human head and neck cancer. The biological activity of Ad released from SELP hydrogels was examined as a function of time to investigate protective effects on viral activity. Antitumor efficacy and viral distribution were investigated for 3 weeks in tumor-bearing mice. Results The encapsulation of Ad with SELP hydrogels sustained biological activity longer than Ad alone. Ad in SELP matrix showed 1.5-fold greater antitumor efficacy compared to that of naked Ad in human xenograft tumor models. Histological analysis demonstrated that treatment with Ad in a SELP matrix resulted in apoptosis in a wider area of tumor tissue and higher density of Ad infection compared to Ad administered alone. Conclusions Matrix-mediated delivery of Ad-containing shRNA with SELP hydrogels enhances therapeutic efficacy by tumor-selective infection, spatio-temporal control and preservation of biologic activity. Copyright (C) 2014 John Wiley & Sons, Ltd. English WILEY-BLACKWELL ELASTINLIKE PROTEIN POLYMERS ENZYME-PRODRUG THERAPY GENE DELIVERY SOLID TUMORS RECOMBINANT ADENOVIRUSES CARCINOMA-CELLS C-MET GROWTH ANGIOGENESIS EXPRESSION Sustained local delivery of oncolytic short hairpin RNA adenoviruses for treatment of head and neck cancer Article 10.1002/jgm.2770 1 JOURNAL OF GENE MEDICINE, v.16, no.5-6, pp.143 - 152 JOURNAL OF GENE MEDICINE 16 5-6 143 152 scie scopus 000340249300004 2-s2.0-84904547250 Biotechnology & Applied Microbiology Genetics & Heredity Medicine, Research & Experimental Biotechnology & Applied Microbiology Genetics & Heredity Research & Experimental Medicine Article ELASTINLIKE PROTEIN POLYMERS ENZYME-PRODRUG THERAPY GENE DELIVERY SOLID TUMORS RECOMBINANT ADENOVIRUSES CARCINOMA-CELLS C-MET GROWTH ANGIOGENESIS EXPRESSION adenovirus head and neck cancer polymeric delivery shRNA