Delivered by Ingenta to: Nanyang Technological University IP: 46.148.30.98 On: Tue, 14 Jun 2016 07:17:30 Copyright: American Scientific Publishers Copyright © 2016 American Scientific Publishers All rights reserved Printed in the United States of America Article Journal of Biomedical Nanotechnology Vol. 12, 781–788, 2016 www.aspbs.com/jbn Selective Laser Ablation of Methicillin-Resistant Staphylococcus Aureus with IgG Functionalized Multi-Walled Carbon Nanotubes Lucian Mocan 1 2 , Ioana Ilie 1 , Flaviu A. Tabaran 3 , Cornel Iancu 1 , Ofelia Mosteanu 1 , Teodora Pop 1 , Claudiu Zdrehus 1 , Dana Bartos 1 , Teodora Mocan 1 2 ∗ , and Cristian Matea 1 3 1 Gastroenterology Institute and “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania 2 Association for Applied Mathematics and Informatics in Research, 3/121 Fabricii Street, 400620 Cluj Napoca, Romania 3 University of Agricultural Sciences and Veterinary Medicine, Faculty of Veterinary Medicine, 400372 Cluj-Napoca, Romania Severe infections caused by Methicillin-resistant Staphylococcus aureus (MRSA) and other bacteria are responsible for millions of deaths each year. One of the main objectives of future antibiotic strategies is to develop new anti-infective agents, which would be highly effective and drug-resistant (antimicrobial resistance being currently exhibited by MRSA), using specific antibodies conjugated to thermally active nanomaterials such as NIR-responsive photothermal contrast agents. Multi-walled carbon nanotubes (MWCNTs) covalently functionalized with immunoglobulin G (IgG, an antagonist of Staphylococcal protein A–SpA, which is a MRSA membrane associated protein) were selectively delivered (at various concentrations and incubation times) into MRSA bacteria. Following treatment, cultures were irradiated using an 808 nm 2 w laser diode. The post irradiation death rate ranged from 39.6% (for 1 mg/L) to 79.2% (for 50 mg/L) at 60 seconds (p< 0001), while at 30 minutes, the death rate increased from 45.2% (1 mg/L) to 85.72% (50 mg/L), p< 0001. Irradiated MRSAs treated with MWCNTs alone (control) for 60 seconds and 30 minutes, at concentrations ranging from 1 mg/L to 50 mg/L, resulted in significantly lower death rates (7.1–34.1% for 60 seconds, 11.7–48.8% for 30 minutes). Using IgG molecules bound to MWCNTs, followed by laser irradiation, we obtained a very efficacious nanoshell-mediated laser therapy of individual MRSA agents providing highly localized killing effects for IgG-MWCNTs targeted bacteria. KEYWORDS: Methicillin-Resistant Staphylococcus Aureus, Carbon Nanotubes, Laser Irradiation, IgG, Photothermal Antimicrobial Nanotherapy. INTRODUCTION Antibiotic resistance, a serious concern in the field of public health, occurs when bacteria cannot be controlled or killed by antibiotics. Millions of patients die every year because of infectious diseases caused by Methicillin- resistant Staphylococcus aureus (MRSA) and many of these deaths are due to organisms that are resistant to antibiotics. 1 Hospital patients are of major concern as two million of them get these bacterial infections each year. Since people with antibiotic-resistant infections are hos- pitalized for a double period of time and die more fre- ∗ Author to whom correspondence should be addressed. Email: teodora.mocan@umfcluj.ro Received: 7 May 2013 Revised/Accepted: 26 November 2013 quently than those whose infections can be treated with medications, there is a huge economic impact of billions of dollars. 2 There is currently less competition and wider spread of MRSA due to the use of broad-spectrum antibiotics that are effective against many different species of bacteria, but not effective against most MRSA strains. MRSA’s resis- tance may be counteracted by antibiotics being developed today, but there is a dire need for better technology that will allow for early detection and treatment of these severe infections. 3 From a clinical point of view, an appealing alterna- tive method of eradicating these MRSA bacteria would be to use agents that physically harm them. The perfect antibacterial treatment in such a context would be tar- geted directly to the infection site, thus targeting particular J. Biomed. Nanotechnol. 2016, Vol. 12, No. 4 1550-7033/2016/12/781/008 doi:10.1166/jbn.2016.2221 781