The major optical absorbers in tissue are melanin and oxy/deoxy-hemoglobin, but the impact of skin tone and pigmentation on biomedical optics is still not completely understood or adequately addressed. Melanin largely governs skin tone with higher melanin concentration in subjects with darker skin tones. Recently, there has been extensive debate on the bias of pulse oximeters when used with darker subjects. Photoacoustic (PA) imaging can measure oxygen saturation similarly as pulse oximeters and could have value in studying this bias. More importantly, it can deconvolute the signal from the skin and underlying tissue. Here, we studied the impact of skin tone on PA signal generation, depth penetration, and oximetry. Our results show that subjects with darker skin tones exhibit significantly higher PA signal at the skin surface, reduced penetration depth, and lower oxygen saturation compared to subjects with lighter skin tones. We then suggest a simple way to compensate for these signal differences.
More recently, we have developed 3D-bioprinted skin-mimicking phantoms with skin colors ranging across the Fitzpatrick scale. These tools can help understand the impact of skin phototypes on biomedical optics. Synthetic melanin nanoparticles of different sizes (70–500 nm) and clusters were fabricated to mimic the optical behavior of melanosome. The absorption coefficient and reduced scattering coefficient of the phantoms are comparable to real human skin. We further validated the melanin content and distribution in the phantoms versus real human skins via photoacoustic (PA) imaging. The PA signal of the phantom could be improved by (i) increasing melanin size (>1,000-fold), (ii) increasing clustering (2–10.5-fold), and (iii) increasing concentration (1.3–8-fold). We then used multiple biomedical optics tools (e.g., PA, fluorescence imaging and photothermal therapy) to understand the impact of skin tone on these modalities. These well-defined 3D-bioprinted phantoms may have value in translating biomedical optics and reducing racial bias.
Bacterial infections lead to high oxidative stress due to production of reactive oxygen species like H2O2 and ONOO- inducing cell damage and death. ROS are a short-lived species making direct, precise and real time measurements difficult. Ag+ is a known bactericidal, disrupting metabolism and disulfide bond formation. In this work we synthesized a thernostic nanoparticle that can measure ROS concentrations and release Ag+ in the presence of ROS. The iodide-doped gold/silver hybrid nanoparticle is 10X more sensitive to H2O2 as compared to silver coated gold nanorods.
Photoacoustic signal can be significantly enhanced by improving the optical absorption, photothermal conversion efficiency, and thermoelastic expansion of an absorbing nanoprobe. Gold nanorods have low photothermal stability leading to spherical deformation and blue-shifting under high fluence lasers. Our work shows enhanced PA signal and high photothermal stability of metal chalcogenide-coated gold nanorods treated with ferricyanide. Preliminary data suggests up to 28 – 48X increase in PA amplitude and over 10X increase in photothermal stability compared to uncoated nanorods.
Ag+ ions are a well-known antibacterial agent, and Ag nanoparticles act as a reservoir of these Ag+ ions for targeted therapy of bacterial infections. However, there are no tools to effectively trigger and monitor the release of Ag+ ions from Ag nanoparticles. Photoacoustic (PA) imaging is an emerging noninvasive imaging tool, and gold nanorods (AuNRs) are an excellent contrast agent for PA imaging. In this work, we developed Au/Ag hybrid nanoparticles by coating AuNRs with silver (Ag), which decreased their photoacoustic signal. The as-prepared, Ag-coated Au nanorods (Au/AgNRs) are stable under ambient conditions, but the addition of ferricyanide solution (1 mM) results in oxidative etching of the silver shell. The PA contrast is simultaneously recovered as the silver is released, and this PA signal offers noninvasive monitoring of localized release of Ag+ ions. The released Ag+ ions exhibit a strong bactericidal efficacy similar to equivalent free Ag+ ions (AgNO3), and the nanoparticles killed >99.99% of both (Gram-positive) methicillin-
resistant Staphylococcus aureus (MRSA, 32 μM Ag+ equivalent) and (Gram-negative) Escherichia coli (8 μM Ag+ equivalent). The theranostic potential of these nanoparticles was demonstrated in a pilot in vivo study. Mice were inoculated with MRSA and Au/AgNRs were subcutaneously implanted followed by silver etching. There was a 730% increase in the PA signal (p < 0.01) pre- and post-etching, and the bacterial counts in infected tissues of the treated group were reduced by 1000-fold (log CFU/g = 4.15 vs 7.75) versus the untreated control; this treatment efficacy was confirmed with histology. We further showed that these hybrid nanoparticles could release Ag+ after stimulation by reactive oxygen species including hydrogen peroxide and peroxynitrite. These hybrid Au/Ag nanoparticles are a useful theranostic agent for the photoacoustic imaging and treatment of bacterial infections.
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