Targeted cancer therapy by immunoconjugated gold-gold sulfide nanoparticles using Protein G as a cofactor.

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.

• Authors: Xinghua Sun, Guandong Zhang, Dhruvinkumar Patel, Dennis Stephens, Andre M Gobin
• Journal: Annals of biomedical engineering (Ann Biomed Eng) Vol. 40 Issue 10 Pg. 2131-9 (Oct 2012) ISSN: 1573-9686 [Electronic] United States
• PMID: 22532323 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Antibodies, Neoplasm
• Antineoplastic Agents
• Bacterial Proteins
• IgG Fc-binding protein, Streptococcus
• Immunoconjugates
• Sulfides
• Gold
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Animals
• Antibodies, Monoclonal, Murine-Derived (chemistry, pharmacology)
• Antibodies, Neoplasm (chemistry, pharmacology)
• Antineoplastic Agents (chemistry, pharmacology)
• Bacterial Proteins (chemistry, pharmacology)
• Breast Neoplasms (drug therapy, pathology)
• Cell Death (drug effects)
• Cell Line, Tumor
• Drug Delivery Systems
• Female
• Gold (chemistry, pharmacology)
• Humans
• Immunoconjugates (chemistry, pharmacology)
• Nanoparticles (chemistry)
• Receptor, ErbB-2 (antagonists & inhibitors, chemistry)
• Sulfides (chemistry, pharmacology)