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: Xin Ming, Lin Wu, Kyle Carver, Ahu Yuan, Yuanzeng Min
• Journal: Nanoscale (Nanoscale) Vol. 7 Issue 29 Pg. 12302-6 (Aug 07 2015) ISSN: 2040-3372 [Electronic] England
• PMID: 26134311 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Dendrimers
• MCL1 protein, human
• Morpholinos
• Myeloid Cell Leukemia Sequence 1 Protein
• Nanoconjugates
• PAMAM Starburst

Topics

• Apoptosis (drug effects)
• Base Sequence
• Cell Line, Tumor
• Dendrimers (chemistry)
• Endocytosis (drug effects)
• Humans
• Microscopy, Confocal
• Morpholinos (chemistry, metabolism, toxicity)
• Myeloid Cell Leukemia Sequence 1 Protein (antagonists & inhibitors, genetics, metabolism)
• Nanoconjugates (chemistry)
• Transfection (methods)