title: Enhanced siRNA delivery using a combination of an arginine-grafted bioreducible polymer, ultrasound, and microbubbles in cancer cells.
abstract: RNAi-based gene therapy for cancer treatment has not shown significant clinical impact due to poor siRNA delivery to the target site. Here, we design a nonviral siRNA gene carrier using a combination of an arginine-grafted bioreducible polymer (ABP), microbubbles (MB), and ultrasound (US), for targeting vascular endothelial growth factor (VEGF) in a human ovarian cancer cell line. Newly designed MBs with a perfluorocrownether gas core show higher stability compared to controls. Further, MBs in combination with polyplexes show a significant higher loading capacity compared to naked siRNA. Lastly, only siRNA-ABP-MB (SAM) complexes in combination with US show significant VEGF knock down in A2780 human ovarian cancer cell line compared to naked siRNA when incubated for a short time after sonication treatment.
authors.affiliation: Center for Controlled Chemical Delivery (CCCD), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, United States.
authors.forename: Stelios
authors.initials: S
authors.lastname: Florinas
authors.forename: Hye Yeong
authors.initials: HY
authors.lastname: Nam
authors.forename: Sung Wan
authors.initials: SW
authors.lastname: Kim
mesh_terms: D001120:Arginine / Q000737:chemistry; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D005260:Female; D055785:Gene Knockdown Techniques; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D045423:Microbubbles; D010051:Ovarian Neoplasms / Q000235:genetics / Q000628:therapy; D011108:Polymers / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D014465:Ultrasonics; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics
chemical_list: D004337:Drug Carriers; D011108:Polymers; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D001120:Arginine