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.

FROM THE CLINICAL EDITOR:

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: Xinghua Sun, Guandong Zhang, Robert S Keynton, Martin G O'Toole, Dhruvinkumar Patel, Andre M Gobin
• Journal: Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 9 Issue 8 Pg. 1214-22 (Nov 2013) ISSN: 1549-9642 [Electronic] United States
• PMID: 23603356 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Immobilized
• Antineoplastic Agents
• Bacterial Proteins
• IgG Fc-binding protein, Streptococcus
• Immunoglobulin G
• Recombinant Proteins
• Polyethylene Glycols
• Gold
• Receptor, ErbB-2

Topics

• Antibodies, Immobilized (chemistry, immunology)
• Antineoplastic Agents (therapeutic use)
• Bacterial Proteins (chemistry)
• Breast (pathology)
• Breast Neoplasms (pathology, therapy)
• Cell Line, Tumor
• Drug Delivery Systems
• Female
• Gold (chemistry, therapeutic use)
• Humans
• Hyperthermia, Induced
• Immunoglobulin G (chemistry, immunology)
• Laser Therapy
• Nanoparticles (chemistry, therapeutic use)
• Polyethylene Glycols (chemistry)
• Receptor, ErbB-2 (immunology)
• Recombinant Proteins (chemistry)