Chitosan hydrogel for localized gene silencing

Hee Dong Han, Edna M. Mora, Ju Won Roh, Masato Nishimura, Sun Joo Lee, Rebecca L. Stone, Menashe Bar-Eli, Gabriel Lopez-Berestein, Anil K. Sood

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To achieve effective delivery of siRNA into target cells in vivo, we have developed a novel approach of siRNA delivery by using local drug delivery systems. Results: The chitosan hydrogel (CH-HG) displayed a liquid-solid phase transition in a temperature-dependent manner and formed an endothermic hydrogel in tumor tissue after intra-tumoral injection. Additionally, we tested the extent of in vivo delivery following a single intra-tumoral injection of Alexa555 siRNA/CH-HG into A375SM-bearing mice. The Alexa555 siRNA demonstrated higher localization into tumor cells compared to control. The Alexa555 siRNA delivery extends to tumor cells outside of CH-HG and some tumor cells also infiltrated into CH-HG. For therapeutic proof-of-concept studies, CH-HG including TG2-targeted siRNA significantly inhibited tumor growth in melanoma (A375SM) and breast (MDA-MB231) tumor models compared to control (A375SM: 72% reduction and MDA-MB231: 92% reduction, p < 0.001). Experimental Design: We prepared a CH-HG system loaded with siRNA to enhance localized therapeutic efficacy without risk for systemic side effects. Delivery of siRNA into CH-HG was confirmed by fluorescence microscopy. Antitumor efficacy was examined in mouse models of melanoma (A375SM) and breast (MDA-MD231) cancer. Conclusions: This study developed a novel local delivery method for siRNA therapy using the CH-HG system. This approach could have broad applications for multiple localized diseases.

Original languageEnglish (US)
Pages (from-to)839-845
Number of pages7
JournalCancer Biology and Therapy
Volume11
Issue number9
DOIs
StatePublished - May 1 2011
Externally publishedYes

Keywords

  • Chitosan
  • Hydrogel
  • Local delivery
  • RNA interference

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Fingerprint Dive into the research topics of 'Chitosan hydrogel for localized gene silencing'. Together they form a unique fingerprint.

Cite this