title: The use of pH-sensitive functional selenium nanoparticles shows enhanced in vivo VEGF-siRNA silencing and fluorescence imaging.
abstract: The utility of small interfering RNAs (siRNAs) has shown great promise in treating a variety of diseases including many types of cancer. While their ability to silence a wide range of target genes underlies their effectiveness, the application of therapies remains hindered by a lack of an effective delivery system. In this study, we sought to develop an siRNA-delivery system for VEGF, a known signaling molecule involved in cancer, that consists of two selenium nanoparticles SeNPs and G2/PAH-Cit/SeNPs. A G2/PAH-Cit/SeNP is a pH-sensitive delivery system that is capable of enhancing siRNA loading, thus increasing siRNA release efficiency and subsequent target gene silencing both in vitro and in vivo. In vivo experiments using G2/PAH-Cit/SeNPs@siRNA led to significantly higher accumulation of siRNA within the tumor itself, VEGF gene silencing, and reduced angiogenesis in the tumor. Furthermore, the G2/PAH-Cit/SeNP delivery system not only enhanced anti-tumor effects on tumor-bearing nude mice as compared to SeNPs@siRNA, but also resulted in weak occurrence of lesions in major target organs. In sum, this study provides a new class of siRNA delivery system, thereby providing an alternative therapeutic route for cancer treatment.
authors.affiliation: Department of Chemistry, Jinan University, Guangzhou 510632, China. tliuliu@jnu.edu.cn.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Yu
authors.forename: Yanan
authors.initials: Y
authors.lastname: Liu
authors.forename: Chengwen
authors.initials: C
authors.lastname: Cao
authors.forename: Fangling
authors.initials: F
authors.lastname: Le
authors.forename: Xiuying
authors.initials: X
authors.lastname: Qin
authors.forename: Dongdong
authors.initials: D
authors.lastname: Sun
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D056945:Hep G2 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016513:Mice, SCID; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism; D009389:Neovascularization, Pathologic; D034741:RNA, Small Interfering / Q000378:metabolism; D012643:Selenium / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry*
chemical_list: D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D012643:Selenium