Theranostic gold-in-gold cage nanoparticles enable photothermal ablation and photoacoustic imaging in biofilm-associated infection models
Maryam Hajfathalian, Christiaan R. de Vries, Jessica C. Hsu, Ahmad Amirshaghaghi, Yuxi C. Dong, Zhi Ren, Yuan Liu, Yue Huang, Yong Li, Simon A.B. Knight, Pallavi Jonnalagadda, Aimen Zlitni, Elizabeth A. Grice, Paul L. Bollyky, Hyun Koo, David P. Cormode
Maryam Hajfathalian, Christiaan R. de Vries, Jessica C. Hsu, Ahmad Amirshaghaghi, Yuxi C. Dong, Zhi Ren, Yuan Liu, Yue Huang, Yong Li, Simon A.B. Knight, Pallavi Jonnalagadda, Aimen Zlitni, Elizabeth A. Grice, Paul L. Bollyky, Hyun Koo, David P. Cormode
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Research Article Infectious disease

Theranostic gold-in-gold cage nanoparticles enable photothermal ablation and photoacoustic imaging in biofilm-associated infection models

Abstract

Biofilms are structured communities of microbial cells embedded in a self-produced matrix of extracellular polymeric substances. Biofilms are associated with many health issues in humans, including chronic wound infections and tooth decay. Current antimicrobials are often incapable of disrupting the polymeric biofilm matrix and reaching the bacteria within. Alternative approaches are needed. Here, we described a complex structure of a dextran-coated gold-in-gold cage nanoparticle that enabled photoacoustic and photothermal properties for biofilm detection and treatment. Activation of these nanoparticles with a near infrared laser could selectively detect and kill biofilm bacteria with precise spatial control and in a short timeframe. We observed a strong biocidal effect against both Streptococcus mutans and Staphylococcus aureus biofilms in mouse models of oral plaque and wound infections, respectively. These effects were over 100 times greater than those seen with chlorhexidine, a conventional antimicrobial agent. Moreover, this approach did not adversely affect surrounding tissues. We concluded that photothermal ablation using theranostic nanoparticles is a rapid, precise, and nontoxic method to detect and treat biofilm-associated infections.

Authors

Maryam Hajfathalian, Christiaan R. de Vries, Jessica C. Hsu, Ahmad Amirshaghaghi, Yuxi C. Dong, Zhi Ren, Yuan Liu, Yue Huang, Yong Li, Simon A.B. Knight, Pallavi Jonnalagadda, Aimen Zlitni, Elizabeth A. Grice, Paul L. Bollyky, Hyun Koo, David P. Cormode

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Figure 4

PTNP efficiently kill biofilm bacteria in vitro.

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PTNP efficiently kill biofilm bacteria in vitro. (A) Schematic of photo ...
(A) Schematic of photo ablation of biofilm with PTNP in wide area mode and (B) precise spatial control mode. The viability of (C) S. mutans and (D) S. aureus within biofilms treated with PTNP and irradiated in wide area mode (n = 5). The statistical technique used in this experiment is a 2-way ANOVA with Šidák’s multiple comparison correction. *P < 0.05, **P < 0.0001. (E–H) Representative confocal micrographs of treated and untreated S. mutans biofilms exposed to wide area mode (Scale bar: 50 μm). Magnified views of S. mutans biofilms in the boxed areas are shown in the bottom left of each panel (Scale bar: 10 μm). Confocal micrograph images of PTNP-treated S. mutans biofilms exposed to laser in precise control mode for (I) 15 seconds, (J) 30 seconds, and (K) 60 seconds. Live bacteria cells (green), dead cells (red), and EPS (purple) are shown (Scale bar: 50 μm). Biofilm bacteria were irradiated at 808 nm (C–H and I–K were irradiated with laser power 0.5 W/cm2 and 2 W/cm2, respectively).