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Gold Nanoparticle-Targeted Laser Therapy for Enhancement of Antibiotic Efficacy against MRSA Biofilms

Lasers are commonly employed in clinical settings for cosmetic dermatology, dentistry, medical imaging, surgery, and photodynamic anti-cancer therapy. The recent explosion of nanotechnology research has paved the way for the development of cutting-edge laser therapies that may overcome some of the limitations of traditional treatments and, thus, greatly expand the use of laser systems by healthcare providers in the future. Newly emerging nanoparticle-targeted laser therapies include targeted destruction of drug-resistant infections, simultaneous imaging and killing of cancer cells (cancer theranostics), and selective delivery of molecules into cells (transfection) for gene therapy or gene knock down.1-3 These applications exploit the unique properties of lasers and nanoparticles for localization and harnessing of light energy at the site of action, generation of photothermal or optoacoustic effects, and delivery of therapeutics or elicitation of effects within tissues in a minimally invasive manner.
Because of these unique properties, nanoparticle-assisted laser therapies have the potential to make a substantial impact in assisting clinicians to overcome the challenges of eradicating recalcitrant infections associated with chronic, nonhealing wounds. Failure to effectively manage chronic infections has largely been attributed to the presence of antibiotic-resistant bacteria and drug-tolerant biofilms, both of which are implicated in 65% to 80% of all human infections.4-6
The problem of genetically-based multidrug resistance mechanisms, such as up-regulation of drug efflux pumps and modification of cellular drug targets, has been recognized and studied for decades.
More recently, scientists and clinicians have realized that bacterial persistence within wounds is also significantly enhanced via formation of biofilms, which typically exhibit a 500- to 5000-fold increase in antibiotic tolerance compared with planktonic (free-floating) cultures.7,8 Biofilm-induced drug tolerance is mainly due to the presence of a dense extracellular matrix that encases the bacteria, functions as an impenetrable barrier against antimicrobials,9 creates a seeding source for recurrent infections, and dissemination throughout the host.10
Unfortunately, the emergence of multidrug resistance increasingly outpaces the discovery and development of new antibiotics,6 and there are no currently approved therapies that specifically target biofilms. A significant gap exists, therefore, for innovative therapies that are less prone to drug resistance and can overcome the challenges caused by the biofilm matrix. 

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