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Abstract
Antimicrobial photodynamic inhibition (aPI) utilizes radical stress generated from the excitation of a photosensitizer (PS) with light to destroy pathogens. Its use against Trichophyton rubrum, a dermatophytic fungus with increasing incidence and resistance, has not been well characterized. Our aim was to evaluate the mechanism of action of aPI against T. rubrum using curcumin as the PS in both free and nanoparticle (curc-np) form. Nanocarriers stabilize curcumin and allow for enhanced solubility and PS delivery. Curcumin aPI, at optimal conditions of 10 μg/mL of PS with 10 J/cm2 of blue light (417 ± 5 nm), completely inhibited fungal growth (p<0.0001) via induction of reactive oxygen (ROS) and nitrogen species (RNS), which was associated with fungal death by apoptosis. Interestingly, only scavengers of RNS impeded aPI efficacy, suggesting that curcumin acts potently via a nitrosative pathway. The curc-np induced greater NO• expression and enhanced apoptosis of fungal cells, highlighting curc-np aPI as a potential treatment for T. rubrum skin infections.
Highlights
Dermatophytic fungi utilize nutrients from keratinized tissue, such as skin, hair and nails, and are the etiologic agents of superficial skin mycoses, known as dermatophytoses [1]
Given the superficial nature of these infections and ease of access by a light source, there has been renewed focus on antimicrobial photodynamic inhibition for fungal infections [9, 10, 11]. aPI is a technique that generates reactive oxygen (ROS) and nitrogen species (RNS) by exciting a pharmacologically inert photosensitizer (PS) with light matched to its absorption wavelength, in the presence of oxygen [12, 13]
A range of curcumin concentrations and blue light doses were evaluated to determine the efficacy of curcumin as a PS and to define the optimal treatment conditions (Table 1)
Summary
Dermatophytic fungi utilize nutrients from keratinized tissue, such as skin, hair and nails, and are the etiologic agents of superficial skin mycoses, known as dermatophytoses [1]. Fungal resistance has been pronounced for Trichophyton rubrum, the most common organism implicated in cutaneous fungal infections [5, 6], and the cause of invasive and recurrent infections in immunocompromised. Given the superficial nature of these infections and ease of access by a light source, there has been renewed focus on antimicrobial photodynamic inhibition (aPI) for fungal infections [9, 10, 11]. API is a technique that generates reactive oxygen (ROS) and nitrogen species (RNS) by exciting a pharmacologically inert photosensitizer (PS) with light matched to its absorption wavelength, in the presence of oxygen [12, 13]. The Type II reaction is more common and involves direct transfer of electrons to ground-state molecular oxygen to produce excited-state singlet oxygen (1O2) [11, 14, 15]. In contrast to conventional antibiotics that target a single pathway, ROS and RNS damage multiple cellular structures, limiting the development of resistance [12, 13, 15]
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