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Targeted Cancer Therapy by Immunoconjugated Gold–Gold Sulfide Nanoparticles Using Protein G as a Cofactor

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Abstract

Gold–gold sulfide nanoparticles (GGS-NPs) fabricated from chloroauric acid and sodium thiosulfate show unique near infrared (NIR) absorption that renders them as a promising candidate for photothermal cancer therapy. To improve targeting efficiency, we developed a versatile method to allow ordered immunoconjugation of antibodies on the surfaces of these nanoparticles via a PEGylated recombinant Protein G (ProG). The PEGylated ProG was prepared with orthopyridyldisulfide-polyethylene glycol-succinimidyl valerate, average MW 2000 (OPSS-PEG-SVA), to first allow the self-assembly of ProG on the nanoparticles, subsequently antibodies were added to this construct to enable active targeting. The bioconjugated GGS-NPs were characterized by TEM, NIR-spectra, dynamic light scattering and modified immunoassay. In in vitro studies, the ProG-conjugated GGS-NPs with bound mouse anti c-erbB-2 (HER-2) immunoglobulin G (IgG) successfully targeted the HER-2 overexpressing breast cancer cell, SK-BR-3. Extensive cell death was observed for the targeted SK-BR-3 line at a low laser power of 540 J (3 W cm−2 for 3 min) while the control breast cancer cell (low expressing HER-2), HTB-22 survived. Using PEGylated ProG as a cofactor for immobilization of antibodies offers a promising strategy to functionalize various IgGs on nanoparticles for engineering their biomedical applications in cancer therapeutics.

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Abbreviations

BSA:

Bovine serum albumin

DI:

Deionized

ELISA:

Enzyme-linked immunosorbent assay

FBS:

Fetal bovine serum

GGS:

Gold-gold sulfide

GNP:

Gold nanoparticle

HER-2:

Human epidermal growth factor receptor-2 (c-erbB-2)

HRP:

Horseradish peroxidase

IgG:

Immunoglobulin G

mPEG:

Monomethoxy polyethylene glycol

MWCO:

Molecular weight cut-off

NIR:

Near infrared

OD:

Optical density

OPSS-PEG-SVA:

Orthopyridyldisulfide-polyethylene glycol-succinimidyl valerate, average MW 2000

PEG:

Polyethylene glycol

ProG:

Protein G

PSG:

Penicillin-streptomycin-glutamine

SEC:

Size exclusion column

STD:

Standard deviation

STEM:

Scanning transmission electron microscope

TMB:

3,3′,5,5′-tetramethylbenzidine dihydrochloride

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Acknowledgments

This work was funded by the grant from Wallace Coulter Foundation: Early Career Phase I award, and NSF-EPSCoR No. 0814194. XS would like to express acknowledge to Marty O’Toole in Bioengineering at the University of Louisville for the assistant on HPLC analysis.

Conflict of Interest

The authors state that they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Bioengineering, University of Louisville, 419 Lutz Hall, Louisville, KY, 40292, USA

    Xinghua Sun, Guandong Zhang, Dhruvinkumar Patel, Dennis Stephens & Andre M. Gobin

Authors
  1. Xinghua Sun
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  2. Guandong Zhang
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  3. Dhruvinkumar Patel
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  4. Dennis Stephens
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  5. Andre M. Gobin
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Corresponding author

Correspondence to Andre M. Gobin.

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Associate Editor James Tunnell oversaw the review of this article.

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Sun, X., Zhang, G., Patel, D. et al. Targeted Cancer Therapy by Immunoconjugated Gold–Gold Sulfide Nanoparticles Using Protein G as a Cofactor. Ann Biomed Eng 40, 2131–2139 (2012). https://doi.org/10.1007/s10439-012-0575-7

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  • DOI: https://doi.org/10.1007/s10439-012-0575-7

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