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Biomacromolecules. 2009 Feb 9;10(2):258-66. doi: 10.1021/bm8009973.

Internally cationic polyamidoamine PAMAM-OH dendrimers for siRNA delivery: effect of the degree of quaternization and cancer targeting.

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1
Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.

Abstract

A novel cancer targeted, internally cationic and surface neutral polyamidoamine (PAMAM) dendrimer, was designed, synthesized, and evaluated as a nanocarrier for the targeted intracellular delivery of siRNA. The dendrimer contained a synthetic analog of Luteinizing hormone-releasing hormone as cancer targeting moiety. The proposed delivery system possesses the following advantages: (1) internal cationic charges for complexation with siRNA and enhanced siRNA protection; (2) low cytotoxicity; (3) lesser degree of quaternization offering free tertiary amines for potential proton sponge effect; and (4) targeting specifically to cancer cells for enhancing siRNA uptake and efficiency and potential limitation of adverse side effects of chemotherapy on healthy organs. Both nontargeted and targeted dendrimer-siRNA complexes formed compact nanometer size spherical particles, exhibited very low cytotoxicity even at the higher concentration, and efficiently penetrated cancer cells in vitro. However, only the targeted dendrimer-siRNA complex was able to substantially decrease the expression of a targeted BCL2 gene.

PMID:
19159248
PMCID:
PMC2653103
DOI:
10.1021/bm8009973
[Indexed for MEDLINE]
Free PMC Article
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