Department of Biological Sciences

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Subject: search.filters.subject.Metal nanoparticles

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    Biosynthesized Protein-Capped Silver Nanoparticles Induce ROS-Dependent Proapoptotic Signals and Prosurvival Autophagy in Cancer Cells
    (ACS, 2017) Panwar, Jitendra; Rahaman, Inamur; Chowdhury, Rajdeep
    In recent years, the use of silver nanoparticles (AgNPs) in biomedical applications has shown an unprecedented boost along with simultaneous expansion of rapid, high-yielding, and sustainable AgNP synthesis methods that can deliver particles with well-defined characteristics. The present study demonstrates the potential of metal-tolerant soil fungal isolate Penicillium shearii AJP05 for the synthesis of protein-capped AgNPs. The particles were characterized using standard techniques, namely, UV–visible spectroscopy, transmission electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The anticancer activity of the biosynthesized AgNPs was analyzed in two different cell types with varied origin, for example, epithelial (hepatoma) and mesenchymal (osteosarcoma). The biological NPs (bAgNPs) with fungal-derived outer protein coat were found to be more cytotoxic than bare bAgNPs or chemically synthesized AgNPs (cAgNPs). Elucidation of the molecular mechanism revealed that bAgNPs induce cytotoxicity through elevation of reactive oxygen species (ROS) levels and induction of apoptosis. Upregulation of autophagy and activation of JNK signaling were found to act as a prosurvival strategy upon bAgNP treatment, whereas ERK signaling served as a prodeath signal. Interestingly, inhibition of autophagy increased the production of ROS, resulting in enhanced cell death. Finally, bAgNPs were also found to sensitize cells with acquired resistance to cisplatin, providing valuable insights into the therapeutic potential of bAgNPs. To the best of our knowledge, this is the first study that provides a holistic idea about the molecular mechanisms behind the cytotoxic activity of protein-capped AgNPs synthesized using a metal-tolerant soil fungus.
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    Superior Bactericidal Efficacy of Fucose-Functionalized Silver Nanoparticles against Pseudomonas aeruginosa PAO1 and Prevention of Its Colonization on Urinary Catheters
    (ACS, 2018-08-10) Panwar, Jitendra
    Pseudomonas aeruginosa, a Gram-negative rod-shaped bacterium is a notorious pathogen causing chronic infections. Its ability to form antibiotic-resistant biofilm has raised the need for the development of alternative treatment approaches. An ideal alternate can be silver nanoparticles known for their strong yet tunable bactericidal activity. However, their use in commercial in vivo medicine could not see the light of the day because of the unwanted toxicity of silver in the host cells at higher concentrations. Thus, strategies which can modulate the bacterial cell–silver nanoparticle interactions thereby reducing the amount of nanoparticles required to kill a typical number of bacterial cells are utmost welcomed. The current work showcases one such strategy by functionalizing the silver nanoparticles with l-fucose to increase their interactions with the LecB lectins present on P. aeruginosa PAO1. The advantage of this approach lies in the higher bactericidal and antibiofilm activity of fucose-functionalized silver nanoparticles (FNPs) as compared to the citrate-capped silver nanoparticles (CNPs) of similar size and concentrations. The superior bactericidal potential of FNPs as demonstrated by fluorescence-assisted cell sorting, confocal laser scanning microscopy, and transmission electron microscopy analyses may be attributed to the higher reactive oxygen species generation and oxidative membrane damage. Additionally, FNPs prevented the formation of biofilms by downregulating the expression of various virulence genes at lower concentrations as compared to CNPs. The practical applicability of the approach was demonstrated by preventing bacterial colonization on artificial silicone rubber surfaces. These results can be extrapolated in the treatment of catheter-associated urinary tract infections caused by P. aeruginosa. In conclusion, the present work strongly advocates the use of antivirulence targets and their corresponding binding residues for the augmentation of the bactericidal effect of silver nanoparticles.