| Summary: | The approaches used for the green biosynthesis of nanoparticles with clinical applications have been widely used in nanotechnology due to their potential to provide safe, eco-friendly, cost effective, high-stability, and high-loading-capacity nanoparticles. This study aimed to evaluate the anti-candidal activity of silver nanoparticles (AgNPs) biosynthesized using the aqueous leaf extract of <i>Calotropis gigantea</i> (CG) alone or in a combination with the plant extract of CG (AgNPs/CG). AgNPs were characterized using UV-Vis spectrophotometry, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and X-ray diffraction (XRD). The results of the standard disk diffusion method revealed that AgNPs alone displayed anti-candidal activity (11.33-mm inhibition zone), while AgNPs/CG displayed a strong synergistic anti-candidal activity (17.76-mm inhibition zone). Similarly, AgNPs/CG completely inhibited the growth of <i>C. albicans</i> after 4 h of incubation, as measured using the time-kill assay. In addition, AgNPs/CG inhibited the dimorphic transition of <i>C. albicans</i> and suppressed both the adhesion and the biofilm formation of <i>C. albicans</i> by 41% and 38%, respectively. The treatment of <i>Candida. albicans</i> with AgNPs/CG showed a significant inhibition of the production of several antioxidant enzymes. Interestingly, AgNPs/CG did not show any cytotoxicity in animal cells, including the MCF-7 cell line and primary mouse bone marrow-derived mesenchymal stem cells (mBMSCs), at the concentration used to completely inhibit the dimorphic transition of <i>C. albicans</i>. In conclusion, we identified AgNPs/CG as a promising natural-product-based nanoparticle that can potentially be used as an anti-candidal drug.
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