title: Dendritic nanoconjugates for intracellular delivery of neutral oligonucleotides.
abstract: Dendrimer-based gene delivery has been constrained by intrinsic toxicity and suboptimal nanostructure. Conjugation of neutral morpholino oligonucleotides (ONs) with PAMAM dendrimers resulted in neutral, uniform, and ultra-small (∼10 nm) nanoconjugates. The nanoconjugates dramatically enhanced cellular delivery of the ONs in cancer cells. After release from the dendrimer in the cytosol, the ONs produced potent functional activity without causing significant cytotoxicity. When carrying an apoptosis-promoting ON, the nanoconjugates produced cancer cell killing directly. Thus, the dendritic nanoconjugates may provide an effective tool for delivering ONs to tumors and other diseased tissues.
authors.affiliation: Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA. xming@email.unc.edu.
authors.forename: Xin
authors.initials: X
authors.lastname: Ming
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.forename: Kyle
authors.initials: K
authors.lastname: Carver
authors.forename: Ahu
authors.initials: A
authors.lastname: Yuan
authors.forename: Yuanzeng
authors.initials: Y
authors.lastname: Min
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry*; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D018613:Microscopy, Confocal; D060172:Morpholinos / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D058726:Nanoconjugates / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D050091:Dendrimers; C579095:MCL1 protein, human; D060172:Morpholinos; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D058726:Nanoconjugates; C104700:PAMAM Starburst