Zhang, C.; Liu, J.; Sun, S.

The increasing prevalence of invasive fungal infections, particularly life-threatening disseminated candidiasis caused by C. albicans, highlights the critical demand for novel therapeutic strategies. This study explores the antifungal potential of curcumin nanosuspension (CNS) alone and in combination with azoles, emphasizing synergistic mechanisms to counter drug resistance. CNS substantially improved curcumin\'s aqueous solubility and enabled sustained in vitro release, overcoming its inherent bioavailability limitations. Checkerboard assays demonstrated synergistic interactions between CNS and fluconazole (FLC) against planktonic cells (FICI: 0.38-0.5) and early-stage C.albicans biofilms (FICI <0.5). Morphological analyses revealed that the combination suppressed hyphal formation and disrupted biofilm architecture--key virulence traits of C. albicans. Mechanistically, qPCR data indicated downregulation of adhesion-related genes (ALS1, ALS3, HWP1, EFG1), impairing fungal colonization. The synergy likely stems from dual mechanisms: facilitated FLC cellular uptake and inhibition of efflux pumps. These findings point out a nanotechnology-driven strategy to revitalize existing azoles through rational combination therapies. The improved bioavailability of CNS and their biofilm-penetrating capacity position this approach as a promising solution for managing refractory candidiasis, offering a pathway to circumvent antifungal resistance.