title: Photothermal killing of Staphylococcus aureus using antibody-targeted gold nanoparticles.
abstract: OBJECTIVE
  The continued emergence of multidrug resistant bacterial infections and the decline in discovery of new antibiotics are major challenges for health care throughout the world. This situation has heightened the need for novel antimicrobial therapies as alternatives to traditional antibiotics. The combination of metallic nanoparticles and laser exposure has been proposed as a strategy to induce physical damage to bacteria, regardless of antibiotic sensitivity. The purpose of this study was to test the antibacterial effect of antibody-targeted gold nanoparticles combined with pulsed laser irradiation.
  
  
  METHODS
  Gold nanoparticles conjugated to antibodies specific to Staphylococcus aureus peptidoglycan were incubated with suspensions of methicillin-resistant and methicillin-sensitive S. aureus (MRSA and MSSA). Bacterial suspensions were then exposed to 8 ns pulsed laser irradiation at a wavelength of 532 nm and fluences ranging from 1 to 5 J/cm(2). Viability of the bacteria following laser exposure was determined using colony forming unit assays. Scanning electron microscopy was used to confirm the binding of nanoparticles to bacteria and the presence of cellular damage.
  
  
  RESULTS
  The laser-activated nanoparticle treatment reduced the surviving population to 31% of control in the MSSA population, while the survival in the MRSA population was reduced to 58% of control. Significant decreases in bacterial viability occurred when the laser fluence exceeded 1 J/cm(2), and this effect was linear from 0 to 5 J/cm(2) (r (2)=0.97). Significantly less bactericidal effect was observed for nonfunctionalized nanoparticles or functionalized nanoparticles without laser activation.
  
  
  CONCLUSIONS
  Laser-activated nanoparticles targeted to S. aureus surface antigens significantly reduced the percentage of viable organisms and represents a promising new treatment modality that could be used either alone or as an adjunct to existing, conventional antibiotic therapy.
authors.affiliation: Maxillofacial Injury and Disease Department, Naval Medical Research Unit San Antonio, Joint Base San Antonio-Fort Sam Houston, TX, USA.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Millenbaugh
authors.affiliation: Maxillofacial Injury and Disease Department, Naval Medical Research Unit San Antonio, Joint Base San Antonio-Fort Sam Houston, TX, USA.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Baskin
authors.affiliation: Maxillofacial Injury and Disease Department, Naval Medical Research Unit San Antonio, Joint Base San Antonio-Fort Sam Houston, TX, USA.
authors.forename: Mauris N
authors.initials: MN
authors.lastname: DeSilva
authors.affiliation: Maxillofacial Injury and Disease Department, Naval Medical Research Unit San Antonio, Joint Base San Antonio-Fort Sam Houston, TX, USA.
authors.forename: W Rowe
authors.initials: WR
authors.lastname: Elliott
authors.affiliation: Department of Ophthalmology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Randolph D
authors.initials: RD
authors.lastname: Glickman
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000907:Antibodies, Bacterial / Q000737:chemistry / Q000494:pharmacology; D006046:Gold / Q000737:chemistry / Q000494:pharmacology; D007834:Lasers; D053768:Metal Nanoparticles / Q000737:chemistry*; D050296:Microbial Viability / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D006046:Gold
keywords: MRSA; bacteria; nanospheres; photoacoustic; pulsed laser
references.citation: J Infect Dis. 2012 Mar 1;205(5):798-806
references.pmid: 22301683
references.citation: J Emerg Med. 2013 Jun;44(6):e397-412
references.pmid: 23466022
references.citation: Lasers Surg Med. 2010 Jan;42(1):38-44
references.pmid: 20077489
references.citation: Br J Pharmacol. 2007 Oct;152(3):299-303
references.pmid: 17618310
references.citation: Int J Nanomedicine. 2010;5:445-54
references.pmid: 20957166
references.citation: PLoS One. 2012;7(9):e45557
references.pmid: 23049814
references.citation: Nano Lett. 2008 Jan;8(1):302-6
references.pmid: 18062714
references.citation: Microb Drug Resist. 2004 Summer;10(2):92-7
references.pmid: 15256023
references.citation: Lasers Surg Med. 2007 Aug;39(7):622-34
references.pmid: 17868103
references.citation: Clin Microbiol Infect. 2013 Jun;19(6):528-36
references.pmid: 22712729
references.citation: Expert Opin Drug Deliv. 2010 May;7(5):577-87
references.pmid: 20345327
references.citation: Nanomedicine (Lond). 2011 Jul;6(5):815-35
references.pmid: 21793674
references.citation: Biochem Biophys Res Commun. 2001 Oct 26;288(2):385-9
references.pmid: 11606054
references.citation: Clin Infect Dis. 2011 Jul 15;53(2):144-9
references.pmid: 21690621
references.citation: Clin Infect Dis. 2008 Jun 1;46 Suppl 5:S368-77
references.pmid: 18462092
references.citation: J Nanosci Nanotechnol. 2009 May;9(5):2841-5
references.pmid: 19452939
references.citation: Biophys J. 2006 Jan 15;90(2):619-27
references.pmid: 16239330
references.citation: Microbiol Immunol. 2009 Sep;53(9):481-6
references.pmid: 19703241
references.citation: Nanomedicine (Lond). 2007 Dec;2(6):777-87
references.pmid: 18095845
references.citation: Chemistry. 2010 May 17;16(19):5600-6
references.pmid: 20397252
references.citation: Nanomedicine (Lond). 2006 Dec;1(4):473-80
references.pmid: 17716149
references.citation: J Phys Chem B. 2006 Apr 13;110(14):7238-48
references.pmid: 16599493
references.citation: Clin Infect Dis. 2008 Jun 1;46 Suppl 5:S344-9
references.pmid: 18462089
references.citation: Int J Microbiol. 2010;2010:null
references.pmid: 20862383
references.citation: J Hosp Infect. 2011 Nov;79(3):189-93
references.pmid: 21741111
references.citation: Emerg Infect Dis. 2009 Sep;15(9):1516-8
references.pmid: 19788830