Hybrid donor-acceptor polymer nanoparticles and combination antibiotic for mitigation of pathogenic bacteria and biofilms

• Published in: Journal of microbiological methods 2021-11, Vol.190, p.106328-106328, Article 106328
• Main Authors: Yates-Alston, Shaina, Sarkar, Santu, Cochran, Matthew, Kuthirummal, Narayanan, Levi, Nicole
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Biofilms; Biofilms - drug effects; Clindamycin - pharmacology; Elastic Modulus - drug effects; Humans; Hyperthermia; Microbial Sensitivity Tests; Microbial Viability; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Photothermal nanoparticles; Polymers - chemistry; Polymers - pharmacology; S. aureus; Staphylococcal Infections - drug therapy; Staphylococcal Infections - microbiology; Staphylococcus aureus - drug effects; Streptococcal Infections - drug therapy; Streptococcal Infections - microbiology; Streptococcus pyogenes - drug effects
• ISSN: 0167-7012; 1872-8359
• DOI: 10.1016/j.mimet.2021.106328

Biofilms pose a significant clinical problem in skin and soft tissue infections. Their resistance to antibiotics has spurred investigations into alternative treatments, such as nanoparticle-mediated photothermal ablation. Non-toxic Hybrid Donor- Acceptor (DA) Polymer nanoParticles (H-DAPPs) were developed for fluorescence imaging (using poly(3-hexylthiophene-2,5 diyl) (P3HT)) and rapid, near-infrared photothermal ablation (NIR- PTA) (using poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b’]dithiophene-2,6-diyl-alt−2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe)). H-DAPPs were evaluated alone, and in combination with antibiotics, against planktonic S. aureus and S. pyogenes, and S. aureus biofilms. H-DAPPs NIR-PTA (15–700 μg/ mL) can generate rapid temperature changes of 27.6–73.1 °C, which can eradicate planktonic bacterial populations and reduce biofilm bacterial viability by more than 4- log (> 99.99%) with exposure to 60 s of 800 nm light. Reductions were confirmed via confocal analysis, which suggested that H-DAPPs PTA caused bacterial inactivation within the biofilms, but did not significantly reduce biofilm polysaccharides. SEM imaging revealed structural changes in biofilms after H-DAPPs PTA. S. aureus biofilms challenged with 100 μg/mL of H-DAPPs (H-DAPPs-100) to induce an average temperature of 55.1 °C, and the minimum biofilm eradication concentration (MBEC) of clindamycin, resulted in up to ~3- log decrease in bacterial viability compared to untreated biofilms and those administered H-DAPPs-100 PTA only, and up to ~2- log compared to biofilms administered only clindamycin. This study demonstrates that polymer nanoparticle PTA can mitigate biofilm infection and may improve antimicrobial efficacy. •The highlights of the manuscript are the synergy of the nanoparticle induced hyperthermia for improving antimicrobial efficacy and the use of PAS-FTIR to characterize chemical changes that occur due to thermal mechanisms.