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Cancer Biol Ther. 2011 May 1;11(9):839-45. Epub 2011 May 1.

Chitosan hydrogel for localized gene silencing.

Author information

1
Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

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.

Comment in

PMID:
21358280
PMCID:
PMC3100632
DOI:
10.4161/cbt.11.9.15185
[Indexed for MEDLINE]
Free PMC Article

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