Dendritic Polyglycerols with Oligoamine Shells Show Low Toxicity and High siRNA Transfection Efficiency in Vitro

RNA interference provides great opportunities for treating diseases from genetic disorders, infection, and cancer. The successful application of small interference RNA (siRNA) in cells with high transfection efficiency and low cytotoxicity is, however, a major challenge in gene-mediated therapy. Sev...

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Bibliographic Details
Published in:Bioconjugate chemistry 2010-10, Vol.21 (10), p.1744-1752
Main Authors: Fischer, Wiebke, Calderón, Marcelo, Schulz, Andrea, Andreou, Ioanna, Weber, Martin, Haag, Rainer
Format: Article
Language:English
Subjects:
Base Sequence
Cancer
Cells
Dendrimers - chemistry
Dendrimers - metabolism
Dendrimers - toxicity
Ethidium - chemistry
Gene therapy
Glycerol - chemistry
HeLa Cells
Humans
Microscopy, Atomic Force
Nitrogen - chemistry
Particle Size
Polyamines - chemistry
Polymers
Polymers - chemistry
Proteins
Ribonucleic acid
RNA
RNA, Small Interfering - genetics
RNA, Small Interfering - metabolism
Surface Properties
Toxicity
Transfection - methods
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Summary:RNA interference provides great opportunities for treating diseases from genetic disorders, infection, and cancer. The successful application of small interference RNA (siRNA) in cells with high transfection efficiency and low cytotoxicity is, however, a major challenge in gene-mediated therapy. Several pH-responsive core shell architectures have been designed that contain a nitrogen shell motif and a polyglycerol core, which has been prepared by a two-step protocol involving the activation of primary and secondary hydroxyl groups by phenyl chloroformate and amine substitution. Each polymer was analyzed by particle size and ζ potential measurements, whereas the respective polyplex formation was determined by ethidium bromide displacement assay, atomic force microscopy (AFM), and surface charge analysis. The in vitro gene silencing properties of the different polymers were evaluated by using a human epithelial carcinoma cell (HeLaS3) line with different proteins (Lamin, CDC2, MAPK2). Polyplexes yielded similar knockdown efficiencies as HiPerFect controls, with comparably low cytotoxicity. Therefore, these efficient and highly biocompatible dendritic polyamines are promising candidates for siRNA delivery in vivo.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc900459n