Sustained local delivery of oncolytic short hairpin RNA adenoviruses for treatment of head and neck cancer

Se Hui Jung, Joung Woo Choi, Chae Ok Yun, Ji Young Yhee, Robert Price, Sun Hwa Kim, Ick Chan Kwon, Hamidreza Ghandehari

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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, spatiotemporal control and preservation of biologic activity.

Original languageEnglish
Pages (from-to)143-152
Number of pages10
JournalJournal of Gene Medicine
Volume16
Issue number5-6
DOIs
Publication statusPublished - 2014 Jan 1
Externally publishedYes

Fingerprint

Head and Neck Neoplasms
Adenoviridae
Small Interfering RNA
Silk
Polymers
Hydrogels
Therapeutics
Neoplasms
Proteins
Genetic Therapy
Biological Preservation
Adenoviridae Infections
Human Adenoviruses
Infection Control
Heterografts
Nude Mice
Apoptosis

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)
  • Drug Discovery

Cite this

Jung, S. H., Choi, J. W., Yun, C. O., Yhee, J. Y., Price, R., Kim, S. H., ... Ghandehari, H. (2014). Sustained local delivery of oncolytic short hairpin RNA adenoviruses for treatment of head and neck cancer. Journal of Gene Medicine, 16(5-6), 143-152. https://doi.org/10.1002/jgm.2770

Sustained local delivery of oncolytic short hairpin RNA adenoviruses for treatment of head and neck cancer. / Jung, Se Hui; Choi, Joung Woo; Yun, Chae Ok; Yhee, Ji Young; Price, Robert; Kim, Sun Hwa; Kwon, Ick Chan; Ghandehari, Hamidreza.

In: Journal of Gene Medicine, Vol. 16, No. 5-6, 01.01.2014, p. 143-152.

Research output: Contribution to journalArticle

Jung, SH, Choi, JW, Yun, CO, Yhee, JY, Price, R, Kim, SH, Kwon, IC & Ghandehari, H 2014, 'Sustained local delivery of oncolytic short hairpin RNA adenoviruses for treatment of head and neck cancer', Journal of Gene Medicine, vol. 16, no. 5-6, pp. 143-152. https://doi.org/10.1002/jgm.2770
Jung, Se Hui ; Choi, Joung Woo ; Yun, Chae Ok ; Yhee, Ji Young ; Price, Robert ; Kim, Sun Hwa ; Kwon, Ick Chan ; Ghandehari, Hamidreza. / Sustained local delivery of oncolytic short hairpin RNA adenoviruses for treatment of head and neck cancer. In: Journal of Gene Medicine. 2014 ; Vol. 16, No. 5-6. pp. 143-152.
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AB - 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, spatiotemporal control and preservation of biologic activity.

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