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

• Published in: Annals of biomedical engineering 2012-10, Vol.40 (10), p.2131-2139
• Main Authors: Sun, Xinghua, Zhang, Guandong, Patel, Dhruvinkumar, Stephens, Dennis, Gobin, Andre M.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal, Murine-Derived - chemistry; Antibodies, Monoclonal, Murine-Derived - pharmacology; Antibodies, Neoplasm - chemistry; Antibodies, Neoplasm - pharmacology; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Bacterial Proteins - chemistry; Bacterial Proteins - pharmacology; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Biophysics; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Death - drug effects; Cell Line, Tumor; Classical Mechanics; Drug Delivery Systems; Female; Gold - chemistry; Gold - pharmacology; Humans; Immunoconjugates - chemistry; Immunoconjugates - pharmacology; Light scattering; Nanoparticles - chemistry; Receptor, ErbB-2 - antagonists & inhibitors; Receptor, ErbB-2 - chemistry; Sulfides; Sulfides - chemistry; Sulfides - pharmacology
• ISSN: 0090-6964; 1573-9686
• DOI: 10.1007/s10439-012-0575-7

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.