title: Ionizable amphiphilic dendrimer-based nanomaterials with alkyl-chain-substituted amines for tunable siRNA delivery to the liver endothelium in vivo.
abstract: A library of dendrimers was synthesized and optimized for targeted small interfering RNA (siRNA) delivery to different cell subpopulations within the liver. Using a combinatorial approach, a library of these nanoparticle-forming materials was produced wherein the free amines on multigenerational poly(amido amine) and poly(propylenimine) dendrimers were substituted with alkyl chains of increasing length, and evaluated for their ability to deliver siRNA to liver cell subpopulations. Interestingly, two lead delivery materials could be formulated in a manner to alter their tissue tropism within the liver-with formulations from the same material capable of preferentially delivering siRNA to 1) endothelial cells, 2) endothelial cells and hepatocytes, or 3) endothelial cells, hepatocytes, and tumor cells in vivo. The ability to broaden or narrow the cellular destination of siRNA within the liver may provide a useful tool to address a range of liver diseases.
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139 (USA).
authors.forename: Omar F
authors.initials: OF
authors.lastname: Khan
authors.forename: Edmond W
authors.initials: EW
authors.lastname: Zaia
authors.forename: Hao
authors.initials: H
authors.lastname: Yin
authors.forename: Roman L
authors.initials: RL
authors.lastname: Bogorad
authors.forename: Jeisa M
authors.initials: JM
authors.lastname: Pelet
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Webber
authors.forename: Iris
authors.initials: I
authors.lastname: Zhuang
authors.forename: James E
authors.initials: JE
authors.lastname: Dahlman
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Anderson
mesh_terms: D000588:Amines / Q000737:chemistry*; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005167:Factor VII / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008099:Liver / Q000166:cytology; D049329:Nanostructures / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*; D014162:Transfection; D000509:alpha-Fetoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000588:Amines; D050091:Dendrimers; D034741:RNA, Small Interfering; D000509:alpha-Fetoproteins; D005167:Factor VII
keywords: RNA; amphiphiles; dendrimers; drug delivery; nanomaterials