Optimization of PAMAM-gold nanoparticle conjugation for gene therapy

Elizabeth R. Figueroa, Adam Y. Lin, Jiaxi Yan, Laureen Luo, Aaron E. Foster, Rebekah A. Drezek

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

The development of efficient and biocompatible non-viral vectors for gene therapy remains a great challenge, and exploiting the properties of both nanoparticle carriers and cationic polymers is an attractive approach. In this work, we have developed gold nanoparticle (AuNP) polyamidoamine (PAMAM) conjugates for use as non-viral transfection agents. AuPAMAM conjugates were prepared by crosslinking PAMAM dendrimers to carboxylic-terminated AuNPs via EDC and sulfo-NHS chemistry. EDC and sulfo-NHS have been utilized widely and in numerous applications such as amino acid coupling; however, their use in the coupling of PAMAM dendrimers to AuNPs presents new challenges to form effective and stable constructs for delivery that have not yet been examined. Enhanced colloidal stability and DNA condensation ability was established by probing two critical synthetic parameters: the reaction rate of the PAMAM crosslinking step, and the amine to carboxyl ratio. Based on this work, increasing the amine to carboxyl ratio during conjugation of PAMAM onto AuNPs yielded the optimal vector with respect to colloidal stability and transfection efficiency invitro. AuPAMAM conjugates present attractive candidates for non-viral gene delivery due to their commercial availability, ease of fabrication and scale-up, high yield, high transfection efficiency and low cytotoxicity.

Original languageEnglish (US)
Pages (from-to)1725-1734
Number of pages10
JournalBiomaterials
Volume35
Issue number5
DOIs
StatePublished - Feb 2014

Keywords

  • Dendrimer
  • DNA
  • Gene therapy
  • Gold
  • Nanocomposite
  • Nanoparticle

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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