The SARS-CoV-2 infections in Indian people have been associated with a mucormycotic fungal infection caused by the filamentous fungi Rhizopus arrhizus. The sporangiospores of R. arrhizus are omnipresent in the environment and cause infection through inhalation or ingestion of contaminated air and foods. Therefore, the anti-sporangiospore activity of polyethyleneimine functionalized silver nanoparticles (PEI-f-Ag-NPs) with variable size and surface charge as a function of the molecular weight of PEI was explored. The results showed that both PEI-f-AgNP-1 and PEI-f-AgNP-2, potentially, attenuated the germination and reduced the viability of sporangiospores. Furthermore, the results showed that the minimum inhibitory concentration (MIC) values of both PEI-f-AgNP-1 and PEI-f-AgNP-2 (1.65 and 6.50 μg/mL, respectively) were dependent on the nanoparticle size and surface ζ potentials. Similarly, the sporangiospore germination inhibition at MIC values was recorded, showing 97.33% and 94% germination inhibition, respectively, by PEI-f-AgNP-1 and 2 within 24 h, respectively. The confocal laser scanning microscopy, SEM-EDS, and confocal Raman spectroscopy investigation of PEI-f-Ag-NPs treated sporangiospores confirmed size and surface charge-dependent killing dynamics in sporangiospores. To the best of our knowledge, this is the first investigation of the polyethyleneimine functionalized silver nanoparticle-mediated size and surface charge-dependent anti-sporangiospore activity against R. arrhizus, along with a possible antifungal mechanism.
Glutathione (GSH) and nickel (II) cation have an indispensable role in various physiological processes, including preventing the oxidative damage of cells and acting as a cofactor for lipid metabolic enzymes. An imbalance in the physiological level of these species may cause serious health complications. Therefore, sensitive and selective fluorescent probes for the detection of GSH and nickel (II) are of great interest for clinical as well as environmental monitoring. Herein, vancomycin-conjugated gold nanoparticles (PEI-AuNP@Van) were prepared and employed for the detection of GSH and nickel (II) based on a turn-on-off mechanism. The as-synthesized PEI-AuNP@Van was ~7.5 nm in size; it exhibited a spherical shape with face-centered cubic lattice symmetry. As compared to vancomycin unconjugated gold nanoparticles, GSH led to the turn-on state of PEI-AuNP@Van, while Ni2+ acted as a fluorescence quencher (turn-off) without the aggregation of nanoparticles. These phenomena strongly justify the active role of vancomycin conjugation for the detection of GSH and Ni2+. The turn-on-off kinetics was linearly proportional over the concentration range between 0.05–0.8 µM and 0.05–6.4 μM. The detection limits were 205.9 and 90.5 nM for GSH and Ni2+, respectively; these results are excellent in comparison to previous reports. This study demonstrates the active role of vancomycin conjugation for sensing of GSH and Ni2+ along with PEI-AuNP@Van as a promising nanoprobe.
The rise of antimicrobial drug resistance among microorganisms presents a global challenge to clinicians. Therefore, it is essential to investigate drug delivery systems to combat resistant bacteria and fungi. This study examined the potential and mode of action of vancomycin-conjugated gold nanoparticles (PEI-AuNP@Van) to enhance vancomycin’s biocidal activity against C. tropicalis, C. albicans, E. coli , and P. aeruginosa . Drug conjugation and nanoparticle characterization were assessed using UV-Vis spectroscopy, X-ray diffraction, TEM, ATR-FTIR, and fluorescence spectroscopy. Effective vancomycin conjugation on polyethyleneimine-stabilized gold nanoparticles was achieved via electrostatic interactions or hydrogen bonding between the COO-/OH groups of vancomycin and the NH- groups of polyethyleneimine, yielding nanoparticles with a narrow size distribution and high zeta potential. The high luminescence of the nanoparticles facilitated their detection in microbial cells. PEI-AuNP@Van was internalized in C. albicans and C. tropicalis but showed surface adsorption in E. coli and P. aeruginosa . The in vitro results indicated that the nanodelivery system exhibited superior biocidal activity against the tested strains compared to free vancomycin and unconjugated AuNPs. The mode of action of PEI-AuNP@Van was cell-type-dependent, involving intracellular reactive oxygen species accumulation, cell membrane integrity loss, and apoptosis. The development of antimicrobial nanoformulations using AuNPs and efficient conjugation systems offers a promising approach to address antimicrobial drug resistance.