title: Enhanced drug delivery via hyperthermal membrane disruption using targeted gold nanoparticles with PEGylated Protein-G as a cofactor.
abstract: Gold nanoparticles (GNPs) with near infrared (NIR) plasmon resonance have been promisingly used in photothermal cancer therapy as a less invasive treatment. Recombinant Protein-G (ProG) was PEGylated to act as a cofactor to immobilize immunoglobulins (IgGs) on GNPs by the Fc region, resulting in optimal orientation of IgGs for efficient cancer targeting. In-vitro studies showed that HER-2 overexpressing breast cancer cells, SK-BR-3, were efficiently targeted and ablated at a laser power of 900 J/cm(2) (5 W/cm(2) for 3 min). However, as a means of enhancing treatment efficacy by increasing cellular sensitivity to chemotherapeutic agents, we showed that GNP exposure to lower power laser resulted in small disruptions of cell membrane due to localized hyperthermia. This did not lead to cell death but provided a mechanism for killing cancer cells by providing enhanced uptake of drug molecules thus leading to a new avenue for hyperthermia-anticancer drug combined cancer therapeutics.
  
  
  BACKGROUND
  PEGylated recombinant Protein-G was used as a cofactor to optimize the orientation of IgGs providing "target seeking" properties to gold nanoparticles used in photothermal cancer therapy. The system demonstrated excellent properties in cancer therapy, with the hope and expectation of future clinical translation.
authors.affiliation: Department of Bioengineering, University of Louisville, Louisville, KY, USA.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Sun
authors.forename: Guandong
authors.initials: G
authors.lastname: Zhang
authors.forename: Robert S
authors.initials: RS
authors.lastname: Keynton
authors.forename: Martin G
authors.initials: MG
authors.lastname: O'Toole
authors.forename: Dhruvinkumar
authors.initials: D
authors.lastname: Patel
authors.forename: Andre M
authors.initials: AM
authors.lastname: Gobin
mesh_terms: D055910:Antibodies, Immobilized / Q000737:chemistry / Q000276:immunology*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000737:chemistry; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005260:Female; D006046:Gold / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D006979:Hyperthermia, Induced; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology; D053685:Laser Therapy; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D055910:Antibodies, Immobilized; D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D006046:Gold; D007074:Immunoglobulin G; D011092:Polyethylene Glycols; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; C034284:IgG Fc-binding protein, Streptococcus
keywords: Cellular uptake and membrane disruption; Gold nanoparticle; Hyperthermia-anticancer drug therapy; PEGylated Protein-G; Targeted cancer therapy