Candidiasis caused by Candida albicans is one of the most common microbial infections. Azoles, polyenes, allylamines, and echinocandins are classes of antifungals used for treating Candida infections. Standard drug doses often become ineffective due to the emergence of multidrug resistance (MDR). This leads to the use of higher drug doses for prolonged duration, resulting in severe toxicity (nephrotoxicity and liver damage) in humans. However, combination therapy using very low concentrations of two or more antifungal agents together, can lower such toxicity and limit evolution of drug resistance. Herein, 4–6 nm zinc oxide quantum dots (ZnO QDs) were synthesized and their in vitro antifungal activities were assessed against drug-susceptible (G1, F1, and GU4) and resistant (G5, F5, and GU5) isolates of C. albicans. In broth microdilution assay, ZnO QDs exhibited dose dependent growth inhibition between 0 – 200 µg/ml and almost 90% growth was inhibited in all Candida strains at 200 µg/ml of ZnO QDs. Synergy between ZnO QDs and antifungal drugs at sub-inhibitory concentrations of each was assessed by checkerboard analysis and expressed in terms of the fractional inhibitory concentration (FIC) index. ZnO QDs were used with two different classes of antifungals (azoles and polyenes) against Candida isolates: combination 1 (with fluconazole); combination 2 (with ketoconazole); combination 3 (with amphotericin B), and combination 4 (with nystatin). Results demonstrated that the potency of combinations of ZnO QDs with antifungal drugs even at very low concentrations of each was higher than their individual activities against the fungal isolates. The FIC index was found to be less than 0.5 for all combinations in the checkerboard assay, which confirmed synergism between sub-inhibitory concentrations of ZnO QDs (25 µg/ml) and individual antifungal drugs. Synergism was further confirmed by spot assay where cell viabilities of Candida strains were significantly reduced in all combinations, which was clearly evident from the disappearance of fungal cells on agar plates containing antifungal combinations. For safer clinical use, the in vitro cytotoxic activity of ZnO QDs was assessed against HeLa cell line and it was found that ZnO QDs were non-toxic at 25 µg/ml. Results suggested that the combination of ZnO QDs with drugs potentiate antimicrobial activity through multitargeted action. ZnO QDs could therefore offer a versatile alternative in combination therapy against MDR fungal pathogens, wherein lowering drug concentrations could reduce toxicity and their multitargeted action could limit evolution of fungal drug resistance.
Nanomaterials are increasingly used as new paradigm for treating infectious diseases, wherein redox perturbation using quantum dots (QDs) show tremendous potential in eliminating various multi-drug resistant microbial pathogens. Herein, spherical, monodispersed ZnO QDs of ~5-6 nm size was synthesized. These ZnO QDs significantly inhibited growth of C. albicans cells. The antifungal action of ZnO QDs against C. albicans involved oxidative stress, mediated via augmentation of endogenous reactive oxygen species (ROS). Further, endogenous ROS production by ZnO QDs and their effect on fungal cell killing was investigated in the presence of antioxidant, ascorbic acid. Results showed that antioxidant failed to offer complete protection against ZnO QDs mediated oxidative stress. It is speculated that intracellular ROS alone is not the only mechanism responsible for ZnO QDs mediated microbial toxicity and other mechanisms probably act either in coordinated or parallel manner to induce cell killing, which merit further investigations for medical adoption of ZnO QDs in biomedicine.
Carbon dots (CDs) are promising new generation bioimaging agents which possess remarkable properties such as excellent biocompatibility, stability, low toxicity, high luminescence, large surface area to volume ratio, flexible surface for conjugations with various biomolecules, tunable size, and optical properties. Among the essential amino acids, phenylalanine was selected for this study. One-pot microwave-assisted method was used to synthesize phenylalanine carbon dots (Phe-CDs) from citric acid and phenylalanine. The UV–visible spectrum of Phe-CDs showed two absorption peaks at 250 and 340 nm depicting the characteristic absorption of an aromatic π system.
Conventional microbiological methods for pathogen detection are time consuming methods and require tedious protocol, expensive instruments, and expert personnel, which delays diagnosis time and treatment. To overcome these limitations, a miniature microfluidic system has been introduced for rapid, sensitive, specific, and easy to handle system for microbial pathogen detection. This miniaturized system uses the dynamics of fluid in microchannels for the collection and detection of pathogen. Microfluidics coupled with a different analytical detection system allow the identification and quantification of whole cells, metabolites, and genetic materials, for accurate diagnosis with all details about microbial pathogen. The high throughput efficiency of a microfluidic system is suitable for point-of-care testing of a broad range of pathogens in even resource-limited facilities/areas. Herein, fundamentals of designing and advances in microfluidic chip integrated with analytical system for pathogen detection are discussed. This review will establish microfluidic as a rapid and accurate point-of-care detection system for microbial pathogens.
L-ascorbic acid (AA) is a hydrophilic, non-toxic, and ROS scavenger. Nano-formulation approaches yield nano-probes with excellent aqueous solubility, low toxicity, biocompatibility, and antioxidant activity. Herein, L-AA was used as carbon source for synthesis of CDs. AA-CDs were synthesized by one step-hydrothermal method, which exhibited strong absorption peak at 340 nm and emission peak at 420 nm. XRD confirmed amorphous nature of AA-CDs. These AA-CDs were biocompatible and also showed negligible toxicity against fungal pathogen (Candida albicans). Further, cellular uptake of AA-CDs was determined by monitoring their internalization into the microbial cells. AA-CDs showed best internalization in 60 minutes. Confocal microscopy images show internalized AA-CDs in the fungal cells, which is visible as bright blue fluorescence inside the cells. We conclude that AA-CDs is eco-friendly and biocompatible nano-probe for bioimaging.
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