title: 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).
  
  
  METHODS
  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.
authors.affiliation: Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Han
authors.forename: Edna M
authors.initials: EM
authors.lastname: Mora
authors.forename: Ju Won
authors.initials: JW
authors.lastname: Roh
authors.forename: Masato
authors.initials: M
authors.lastname: Nishimura
authors.forename: Sun Joo
authors.initials: SJ
authors.lastname: Lee
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Stone
authors.forename: Menashe
authors.initials: M
authors.lastname: Bar-Eli
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lopez-Berestein
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000628:therapy*; D045744:Cell Line, Tumor; D048271:Chitosan / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage*; D008545:Melanoma / Q000235:genetics / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D020100:Hydrogels; D034741:RNA, Small Interfering; D048271:Chitosan