Optimization of PAMAM-gold nanoparticle conjugation for gene therapy

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 (...

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Bibliographic Details
Published inBiomaterials Vol. 35; no. 5; pp. 1725 - 1734
Main Authors Figueroa, Elizabeth R, Lin, Adam Y, Yan, Jiaxi, Luo, Laureen, Foster, Aaron E, Drezek, Rebekah A
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Ltd 01.02.2014
Subjects
Advanced Basic Science
Cell Line
Dendrimer
Dendrimers - chemical synthesis
Dendrimers - chemistry
Dentistry
DNA
Gene therapy
Genetic Therapy
Gold
Gold - chemistry
Humans
Metal Nanoparticles
Microscopy, Electron, Transmission
Nanocomposite
Nanoparticle
Spectrophotometry, Ultraviolet
Transfection
Gold
Dendrimer
Nanocomposite
Gene therapy
Nanoparticle
DNA
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Summary: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 in vitro . 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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2013.11.026