Internally cationic polyamidoamine PAMAM-OH dendrimers for siRNA delivery: Effect of the degree of Quaternization and cancer targeting

Mahesh L. Patil, Min Zhang, Oleh Taratula, Olga B. Garbuzenko, Huixin He, Tamara Minko

Research output: Contribution to journalArticlepeer-review

190 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)258-266
Number of pages9
JournalBiomacromolecules
Volume10
Issue number2
DOIs
StatePublished - Feb 9 2009

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biomaterials
  • Polymers and Plastics
  • Materials Chemistry

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