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The increased incidence of antibiotic-resistant gram-positive bacteria, like methicillin-resistant S. aureus (MRSA), necessitates treatments that eliminate the potential of developing further resistance. Antimicrobial photodynamic therapy (aPDT) has shown promise as gram-positive infections can be specifically photosensitized by inducing the accumulation of coproporphyrin III (CPIII) through the administration of VU0038882 (‘882), a small-molecule activator of coproporphyrinogen oxidase, and delta-aminolevulinic acid hydrochloride (ALA). While the phototoxic effects of CPIII are most pronounced when stimulated with 395nm light, corresponding to its Soret absorption-band, the high absorption of the skin at that wavelength reduces the efficacy in vivo by three orders of magnitude as compared to in vitro. Although the issue of light penetrance can be mitigated by using red-shifted wavelengths targeting the Q-bands of CPIII (λpeak=498/530/565/619nm), the efficiency of cytotoxic reactive oxygen species (ROS) production and bacterial killing drastically reduces. Though this inefficiency can be partially overcome through an increased light dose, photoinactivation of CPIII and oxygen depletion limits this process to a maximum effective light dose. To overcome these limitations and improve the overall efficacy of CPIII-targeted aPDT, we designed and built a novel multi-LED light source and explored the effect of simultaneously targeting the Soret-band and Q-bands. We present that lower radiant exposures of blue light in conjunction with a higher exposure of green or red light increases the amount of bacterial killing by 1 to 3 logs in vitro as compared to either treatment alone. This enhancement is expected to increase when utilized in vivo due to differences in penetrance.
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