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NANOPARTICLE TREATMENT MODALITIES FOR MITIGATING PATHOGENIC BACTERIA AND BIOFILMS

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abstract
Biofilms pose a significant clinical problem in skin and soft tissue infections.Despite clinical standards for treating these virulent microbial structures, biofilms remain extremely common and difficult to eradicate. Their inherent resistance to treatment (like antibiotic exposure) has spurred investigations into alternative treatment modalities. Nanoparticle-mediated photothermal ablation has become a novel modality for application in fighting pathogenic biofilms. Organic donor-acceptor (D-A) conjugated polymer nanoparticles (CPNP) may be more efficient and stable than metal and more biocompatible than carbon. Here, we present a formulation of D-A CPNPs called PolyDOTS for rapid, near-infrared photothermal ablation (NIR-PTA) and combined antibiotic treatment against pathogenic bacteria and biofilms. We show that PolyDOTS absorb in the near-infrared range (NIR) for heat generation and fluorescence under visible light stimulation. Herein, we demonstrate how PolyDOTS have good photothermal conversion efficiency and exhibit exceptional heat generation. We show that PolyDOTS NIR-PTA can eradicate bacterial populations and reduce biofilm bacterial viability by more than 4- log ( > 99.99%), after exposure to 60 seconds of focal hyperthermia, between 50.6 and 57.3°C. Reductions were confirmed via LIVE/DEAD confocal analysis, which suggested that the treatment may have caused bacterial inactivation within the biofilms. COMSTAT analysis indicated that PolyDOTS PTA resulted in reductions in biofilm biomass, while confocal analysis of biofilm extracellular matrix (ECM) suggested that the treatment did not significantly reduce polysaccharides. SEM imaging revealed increasingly pronounced aggregation, and previously unobserved structural changes to the ECM after PolyDOTS PTA. S. aureus biofilms challenged with 100 µg/mL of PolyDOTS (PD-100) and the minimal biofilm eradication concentration (MBEC) of clindamycin, resulted in up to ~ 3- log decrease in bacterial viability compared to untreated biofilms and those administered PD-100 PTA only, and up to ~ 2- log compared to biofilms administered only MBEC treatment. SEM imaging of the treatments indicated that morphological and structural changes induced by PolyDOTS PTA might be reversible, but regrowth is limited after treatment. This study provides evidence that polymer nanoparticle PTA can successfully mitigate biofilm infection and improve existing treatment by enhancing antimicrobial efficacy.
subject
Biofilm
Hyperthermia
Infectious Disease
Nanoparticles
Polymers
Thermal Therapy
contributor
Yates-Alston, Shaina Aleese (author)
Levi-Polyachenko, Nicole H (committee chair)
Ornelles, David A (committee member)
Palavecino, Elizabeth L (committee member)
Vlad, Lucian G (committee member)
Seeds, Michael C (committee member)
date
2021-06-03T08:36:17Z (accessioned)
2021 (issued)
degree
Molecular Medicine and Translational Science (discipline)
2022-06-02 (liftdate)
embargo
2022-06-02 (terms)
identifier
http://hdl.handle.net/10339/98831 (uri)
language
en (iso)
publisher
Wake Forest University
title
NANOPARTICLE TREATMENT MODALITIES FOR MITIGATING PATHOGENIC BACTERIA AND BIOFILMS
type
Dissertation

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