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

doi:10.1016/j.biomaterials.2013.11.026

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

Houston Methodist

Research output: Contribution to journal › Article › peer-review

82 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 language	English (US)
Pages (from-to)	1725-1734
Number of pages	10
Journal	Biomaterials
Volume	35
Issue number	5
DOIs	https://doi.org/10.1016/j.biomaterials.2013.11.026
State	Published - 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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10.1016/j.biomaterials.2013.11.026

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@article{209c2491736a4e4cbc62869639c87554,

title = "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 (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.",

keywords = "Dendrimer, DNA, Gene therapy, Gold, Nanocomposite, Nanoparticle",

author = "Figueroa, {Elizabeth R.} and Lin, {Adam Y.} and Jiaxi Yan and Laureen Luo and Foster, {Aaron E.} and Drezek, {Rebekah A.}",

note = "Funding Information: This work was supported by a pre-doctoral fellowship from the Ford Foundation, a training fellowship from the Keck Center of the Gulf Coast Consortia, on the Nanobiology Interdisciplinary Graduate Training Program, National Institute of Biomedical Imaging and Bioengineering (NIBIB) (T32EB009379, contact PI Rebekah Drezek), the Medical Scientist Training Program at Baylor College of Medicine, the Edward and Josephine Hudson Scholarship, the Ruth L. Kirschstein National Research Service Awards for Individual Predoctoral MD/PhD Fellows (F30CA165686-01A1) by the National Institute of Health (NIH) and National Cancer Institute (NCI), the Welch Foundation (C-1598), and the NIH (R01 CA172836). We would like to thank Clark Needham and Ryan Schweller for donating plasmids and for their advice, Veronica Leautaud and the Richards-Kortum Lab for use of their UV transilluminator, and Denise Benoit and the Colvin Lab for training and for use of their TOC instrument. The authors confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. ",

year = "2014",

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doi = "10.1016/j.biomaterials.2013.11.026",

language = "English (US)",

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pages = "1725--1734",

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AU - Figueroa, Elizabeth R.

AU - Lin, Adam Y.

AU - Yan, Jiaxi

AU - Luo, Laureen

AU - Foster, Aaron E.

AU - Drezek, Rebekah A.

N1 - Funding Information: This work was supported by a pre-doctoral fellowship from the Ford Foundation, a training fellowship from the Keck Center of the Gulf Coast Consortia, on the Nanobiology Interdisciplinary Graduate Training Program, National Institute of Biomedical Imaging and Bioengineering (NIBIB) (T32EB009379, contact PI Rebekah Drezek), the Medical Scientist Training Program at Baylor College of Medicine, the Edward and Josephine Hudson Scholarship, the Ruth L. Kirschstein National Research Service Awards for Individual Predoctoral MD/PhD Fellows (F30CA165686-01A1) by the National Institute of Health (NIH) and National Cancer Institute (NCI), the Welch Foundation (C-1598), and the NIH (R01 CA172836). We would like to thank Clark Needham and Ryan Schweller for donating plasmids and for their advice, Veronica Leautaud and the Richards-Kortum Lab for use of their UV transilluminator, and Denise Benoit and the Colvin Lab for training and for use of their TOC instrument. The authors confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

PY - 2014/2

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N2 - 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.

AB - 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.

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Optimization of PAMAM-gold nanoparticle conjugation for gene therapy

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Keywords

ASJC Scopus subject areas

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