Chitosan hydrogel for localized gene silencing

• Published in: Cancer biology & therapy 2011-05, Vol.11 (9), p.839-845
• Main Authors: Han, Hee Dong, Mora, Edna M., Roh, Ju Won, Nishimura, Masato, Lee, Sun Joo, Stone, Rebecca L., Bar-Eli, Menashe, Lopez-Berestein, Gabriel, Sood, Anil K
• Format: Article
• Language: English
• Subjects: Animals; Binding; Biology; Bioscience; Breast Neoplasms - genetics; Breast Neoplasms - therapy; Calcium; Cancer; Cell; Cell Line, Tumor; Chitosan - administration & dosage; Cycle; Drug Delivery Systems - methods; Female; Gene Silencing; Humans; Hydrogels - administration & dosage; Landes; Melanoma - genetics; Melanoma - therapy; Mice; Mice, Nude; Organogenesis; Proteins; Research Paper; RNA, Small Interfering - administration & dosage; RNA, Small Interfering - genetics; Xenograft Model Antitumor Assays
• ISSN: 1538-4047; 1555-8576
• DOI: 10.4161/cbt.11.9.15185

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