Chitosan hydrogel for localized gene silencing.

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.

journal_name

Cancer Biol Ther

journal_title

Cancer biology & therapy

authors

Han HD,Mora EM,Roh JW,Nishimura M,Lee SJ,Stone RL,Bar-Eli M,Lopez-Berestein G,Sood AK

doi

10.4161/cbt.11.9.15185

subject

Has Abstract

pub_date

2011-05-01 00:00:00

pages

839-45

issue

9

eissn

1538-4047

issn

1555-8576

pii

15185

journal_volume

11

pub_type

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