(WHS-K1.05) DETECTION AND PHOTOABLATION OF WOUND BIOFILM INFECTIONS WITH THERANOSTIC GOLD-IN-GOLD CAGE NANOPARTICLES
Thursday, May 16, 2024
9:15 AM – 10:15 AM East Coast USA Time
Introduction Bacterial biofilms colonize wounds and delay healing. These biofilms are difficult to treat with existing clinical therapies due to antimicrobial resistance. Therefore, a critical need exists to effectively diagnose and treat biofilm infections. Here, we present a theranostic agent to image and treat harmful biofilms. We developed gold-in-gold cage nanoparticles (PTNP) with enhanced photothermal (PTT) and photoacoustic imaging (PA) properties that are promising candidates for biofilm detection, treatment, and infectious disease control. We found PTNP can control virulent biofilms and treat infectious disease via activation with near infrared region (NIR) laser with precise spatial control and in a short timeframe. A strong biocidal effect against Staphylococcus aureus (S. aureus) within biofilms was observed, considerably more effective than currently clinically used skin antimicrobials. Therefore, here, we introduce a fast, precise, and unique topical therapeutic method to image and treat costly skin biofilm-associated infections. Methods PTNP were synthesized via galvanic replacement reaction.1 After purification, the collected nanoparticles were coated with dextran-10kDa (DEX) to provide stability in biological media. These structures were characterized using transition electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), and UV-visible spectroscopy. The anti-biofilm efficacy of the PTNP was examined in vitro using S. aureus biofilms. The untreated or treated biofilm with PTNP was analyzed using high-resolution confocal fluorescence imaging, while PA imaging of biofilms treated with PTNP was carried out to investigate the theranostic potential of these structures within the biofilm in vivo. Furthermore, PTNP was examined for its efficacy as an anti-biofilm agent to control, image, and treat wound infections. Results TEM of PTNP showed the Au seeds core and the shells that contain AuAg alloys with some porosities. The optical extinction spectra of PTNP showed the plasmonic peak at 808 nm. Uptake of PTNP by S. aureus biofilms was confirmed by SEM in backscattered electron (BSE) mode which showing the morphology of PTNP-treated biofilm. We found almost complete bacteria killing in biofilms incubated with PTNP and after 30 s laser irradiation, while no dead cells were observed in the area without laser irradiation. We found an exceptionally strong biocidal effect against S. aureus within biofilms when exposed to NIR laser irradiation and PTNP. Treatment of S. aureus infected mouse wounds was studied using bioluminescence imaging (BLI), which showed potent in vivo bacterial killing. Robust PA contrast can be seen in wound infection treated with PTNP. Conclusion PTNP is a promising approach as a theranostic anti-biofilm agent. References 1. Hajfathalian, M., et al., J Clin Invest 2023, 133 (21).