Nanoparticle-Based Photodynamic Inhibition of Candida albicans Biofilms with Interfering Quorum Sensing

Biofilm formation is a critical event in the pathogenesis and virulence of fungal infections caused by Candida albicans, giving rise to about a 1000-fold increase in the resistance to antifungal agents. Although photodynamic treatment (PDT) has been excellently implicated in bacterial infections, studies on its potential against fungal infection through the clearance of fungal biofilm formation remain at its infancy stage. Here, we have designed photodynamic nanoparticles with different sizes, modifications, and the ability of generating reactive oxygen species (ROS) to examine their effects on inhibiting biofilm formation and destructing mature biofilms of C. albicans. We found that the nanoparticles modified with oligo-chitosan exhibited a better binding efficiency for planktonic cells, leading to stronger inhibitory efficacy of the filamentation and the early-stage biofilm formation. However, for mature biofilms, the nanoparticles with the smallest size (∼15 nm) showed the fastest penetration speed and a pronounced destructing effect albeit conferring the lowest ROS-producing capability. The inhibitory effect of photodynamic nanoparticles was dependent on the disruption of fungal quorum sensing (QS) by the upregulation of QS molecules, farnesol and tyrosol, mediated through the upregulation of ARO 8 and DPP 3 expression. Our findings provide a powerful strategy of nanoparticulate PDT to combat fungal infections through the inhibition of both hyphal and biofilm formation by disrupting QS.