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.
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.
Authors: Premal H Thaker; Liz Y Han; Aparna A Kamat; Jesusa M Arevalo; Rie Takahashi; Chunhua Lu; Nicholas B Jennings; Guillermo Armaiz-Pena; James A Bankson; Murali Ravoori; William M Merritt; Yvonne G Lin; Lingegowda S Mangala; Tae Jin Kim; Robert L Coleman; Charles N Landen; Yang Li; Edward Felix; Angela M Sanguino; Robert A Newman; Mary Lloyd; David M Gershenson; Vikas Kundra; Gabriel Lopez-Berestein; Susan K Lutgendorf; Steven W Cole; Anil K Sood Journal: Nat Med Date: 2006-07-23 Impact factor: 53.440
Authors: Amit Verma; Huamin Wang; Bramanandam Manavathi; Jansina Y Fok; Aman P Mann; Rakesh Kumar; Kapil Mehta Journal: Cancer Res Date: 2006-11-01 Impact factor: 12.701
Authors: Charles N Landen; Arturo Chavez-Reyes; Corazon Bucana; Rosemarie Schmandt; Michael T Deavers; Gabriel Lopez-Berestein; Anil K Sood Journal: Cancer Res Date: 2005-08-01 Impact factor: 12.701
Authors: Jee Young Hwang; Lingegowda S Mangala; Jansina Y Fok; Yvonne G Lin; William M Merritt; Whitney A Spannuth; Alpa M Nick; Derek J Fiterman; Pablo E Vivas-Mejia; Michael T Deavers; Robert L Coleman; Gabriel Lopez-Berestein; Kapil Mehta; Anil K Sood Journal: Cancer Res Date: 2008-07-15 Impact factor: 12.701
Authors: Angela J Ziebarth; Somaira Nowsheen; Adam D Steg; Monjri M Shah; Ashwini A Katre; Zachary C Dobbin; Hee-Dong Han; Gabriel Lopez-Berestein; Anil K Sood; Michael Conner; Eddy S Yang; Charles N Landen Journal: Clin Cancer Res Date: 2012-11-12 Impact factor: 12.531
Authors: David G Menter; Sherri L Patterson; Craig D Logsdon; Scott Kopetz; Anil K Sood; Ernest T Hawk Journal: Cancer Prev Res (Phila) Date: 2014-07-24
Authors: Christopher E Nelson; Arnold J Kim; Elizabeth J Adolph; Mukesh K Gupta; Fang Yu; Kyle M Hocking; Jeffrey M Davidson; Scott A Guelcher; Craig L Duvall Journal: Adv Mater Date: 2013-12-16 Impact factor: 30.849