title: 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.affiliation: Department of Bioengineering, University of Louisville, KY 40292, USA.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Sun
authors.forename: Guandong
authors.initials: G
authors.lastname: Zhang
authors.forename: Dhruvinkumar
authors.initials: D
authors.lastname: Patel
authors.forename: Dennis
authors.initials: D
authors.lastname: Stephens
authors.forename: Andre M
authors.initials: AM
authors.lastname: Gobin
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000737:chemistry / Q000494:pharmacology; D000912:Antibodies, Neoplasm / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005260:Female; D006046:Gold / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013440:Sulfides / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D006046:Gold; D018796:Immunoconjugates; D018719:Erb-b2 Receptor Tyrosine Kinases; D013440:Sulfides; C034284:IgG Fc-binding protein, Streptococcus; C508053:ERBB2 protein, human