Chitosan hydrogel for localized gene silencing

Cancer Biol Ther. 2011 May 1;11(9):839-45. doi: 10.4161/cbt.11.9.15185. Epub 2011 May 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / therapy*
  • Cell Line, Tumor
  • Chitosan / administration & dosage*
  • Drug Delivery Systems / methods*
  • Female
  • Gene Silencing*
  • Humans
  • Hydrogels / administration & dosage*
  • Melanoma / genetics
  • Melanoma / therapy*
  • Mice
  • Mice, Nude
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics
  • Xenograft Model Antitumor Assays


  • Hydrogels
  • RNA, Small Interfering
  • Chitosan