Ultrasound-assisted siRNA delivery via arginine-grafted bioreducible polymer and microbubbles targeting VEGF for ovarian cancer treatment

JOURNAL OF CONTROLLED RELEASE

卷:183

Article

Florinas, Stelios¹  Kim, Jaesung¹  Nam, Kihoon¹  Janat-Amsbury, Margit M.^1,2  Kim, Sung Wan¹ 

[1] Univ Utah, Ctr Controlled Chem Delivery, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84108 USA

[2] Univ Utah, Dept Obstet & Gynecol, Div Gynecol Oncol, Salt Lake City, UT 84132 USA

关键词: siRNA;    Ultrasound;    Microbubbles;    RNAi;    VEGF;    Cancer;   

DOI  :  10.1016/j.jconrel.2014.03.025

来源: Elsevier

【 摘 要 】

The major drawback hampering siRNA therapies from being more widely accepted in clinical practice is its insufficient accumulation at the target site mainly due to poor cellular uptake and rapid degradation in serum. Therefore, we designed a novel polymeric siRNA carrier system, which would withstand serum-containing environments and tested its performance in vitro as well as in vivo. Delivering siRNA with a system combining an arginine-grafted bioreducible polymer (ABP), microbubbles (MBs), and ultrasound technology (US) we were able to synergize the advantages each delivery system owns individually, and created our innovative siRNA-ABP-MB (SAM) complexes. SAM complexes show significantly higher siRNA uptake and VEGF protein knockdown in vitro with serum-containing media when compared to naked siRNA, and 25 k-branched-polyethylenimine (bPEI) representing the current standard in nonviral gene therapy. SAM complexes activated by US are also able to improve siRNA uptake in tumor tissue resulting in decelerating tumor growth in vivo. (C) 2014 Elsevier B.V. All rights reserved.

【 授权许可】

Free