Publications by authors named "Pritam Biswas"

9 Publications

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Redox Buffering Capacity of Nanomaterials as an Index of ROS-Based Therapeutics and Toxicity: A Preclinical Animal Study.

ACS Biomater Sci Eng 2021 Jun 1;7(6):2475-2484. Epub 2021 Jun 1.

Department of Chemical, Biological and Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector 3, Salt Lake, Kolkata 700106, India.

Precise control of intracellular redox status, i.e., maintenance of the physiological level of reactive oxygen species (ROS) for mediating normal cellular functions (oxidative eustress) while evading the excess ROS stress (distress), is central to the concept of redox medicine. In this regard, engineered nanoparticles with unique ROS generation, transition, and depletion functions have the potential to be the choice of redox therapeutics. However, it is always challenging to estimate whether ROS-induced intracellular events are beneficial or deleterious to the cell. Here, we propose the concept of redox buffering capacity as a therapeutic index of engineered nanomaterials. As a steady redox state is maintained for normal functioning cells, we hypothesize that the ability of a nanomaterial to preserve this homeostatic condition will dictate its therapeutic efficacy. Additionally, the redox buffering capacity is expected to provide information about the nanoparticle toxicity. Here, using citrate-functionalized trimanganese tetroxide nanoparticles (C-MnO NPs) as a model nanosystem, we explored its redox buffering capacity in erythrocytes. Furthermore, we went on to study the chronic toxic effect (if any) of this nanomaterial in the animal model to co-relate with the experimentally estimated redox buffering capacity. This study could function as a framework for assessing the capability of a nanomaterial as redox medicine (whether maintains eustress or damages by creating distress), thus orienting its application and safety for clinical use.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00402DOI Listing
June 2021

Incorporation of a Biocompatible Nanozyme in Cellular Antioxidant Enzyme Cascade Reverses Huntington's Like Disorder in Preclinical Model.

Adv Healthc Mater 2021 04 16;10(7):e2001736. Epub 2020 Dec 16.

Department of Chemical, Biological and Macromolecular Sciences, S. N. Bose National Centre for Basic Sciences, Block JD, Sector 3, Salt Lake, Kolkata, 700106, India.

The potentiality of nano-enzymes in therapeutic use has directed contemporary research to develop a substitute for natural enzymes, which are suffering from several disadvantages including low stability, high cost, and difficulty in storage. However, inherent toxicity, inefficiency in the physiological milieu, and incompatibility to function in cellular enzyme networks limit the therapeutic use of nanozymes in living systems. Here, it is shown that citrate functionalized manganese-based biocompatible nanoscale material (C-Mn O NP) efficiently mimics glutathione peroxidase (GPx) enzyme in the physiological milieu and easily incorporates into the cellular multienzyme cascade for H O scavenging. A detailed computational study reveals the mechanism of the nanozyme action. The in vivo therapeutic efficacy of C-Mn O nanozyme is further established in a preclinical animal model of Huntington's disease (HD), a prevalent progressive neurodegenerative disorder, which has no effective medication to date. Management of HD in preclinical animal trial using a biocompatible (non-toxic) nanozyme as a part of the metabolic network may uncover a new paradigm in nanozyme based therapeutic strategy.
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http://dx.doi.org/10.1002/adhm.202001736DOI Listing
April 2021

Flexibility modulates the catalytic activity of a thermostable enzyme: key information from optical spectroscopy and molecular dynamics simulation.

Soft Matter 2020 Mar 5;16(12):3050-3062. Epub 2020 Mar 5.

Department of Microbiology, St. Xavier's College, 30, Mother Teresa Sarani, Kolkata 700016, India.

Enzymes are dynamical macromolecules and their conformation can be altered via local fluctuations of side chains, large scale loop and even domain motions which are intimately linked to their function. Herein, we have addressed the role of dynamic flexibility in the catalytic activity of a thermostable enzyme almond beta-glucosidase (BGL). Optical spectroscopy and classical molecular dynamics (MD) simulation were employed to study the thermal stability, catalytic activity and dynamical flexibility of the enzyme. An enzyme assay reveals high thermal stability and optimum catalytic activity at 333 K. Polarization-gated fluorescence anisotropy measurements employing 8-anilino-1-napthelenesulfonic acid (ANS) have indicated increasing flexibility of the enzyme with an increase in temperature. A study of the atomic 3D structure of the enzyme shows the presence of four loop regions (LRs) strategically placed over the catalytic barrel as a lid. MD simulations have indicated that the flexibility of BGL increases concurrently with temperature through different fluctuating characteristics of the enzyme's LRs. Principal Component Analysis (PCA) and the Steered Molecular Dynamics (SMD) simulation manifest the gatekeeper role of the four LRs through their dynamic fluctuations surrounding the active site which controls the catalytic activity of BGL.
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http://dx.doi.org/10.1039/c9sm02479dDOI Listing
March 2020

A Smart Nanotherapeutic Agent for in vitro and in vivo Reversal of Heavy-Metal-Induced Causality: Key Information from Optical Spectroscopy.

ChemMedChem 2020 03 27;15(5):420-429. Epub 2019 Dec 27.

Department of Chemical, Biological and Macromolecular Sciences, SN Bose National Centre for Basic Sciences Block JD, Sector 3, Salt Lake, Kolkata, 700106, India.

Human exposure to heavy metals can cause a variety of life-threatening disorders, affecting almost every organ of the body, including the nervous, circulatory, cardiac, excretory, and hepatic systems. The presence of heavy metal (cause) and induced oxidative stress (effect) are both responsible for the observed toxic effects. The conventional and effective way to combat heavy metal overload diseases is through use of metal chelators. However, they possess several side effects and most importantly they fail to manage the entire causality. In this study, we introduce citrate-functionalized Mn O nanoparticles (C-Mn O NPs) as an efficient chelating agent for treatment of heavy metal overload diseases. By means of UV/Vis absorbance and steady-state fluorescence spectroscopic techniques we investigated the efficacy of the NPs in chelation of a model heavy metal, lead (Pb). We also explored the retention of antioxidant properties of the Pb-chelated C-Mn O NPs using a UV/Vis-assisted DPPH assay. Through CD spectroscopic studies we established that the NPs can reverse the Pb-induced structural modifications of biological macromolecules. We also studied the in vivo efficacy of NPs in Pb-intoxicated C57BL/6j mice. The NPs were not only able to mobilize the Pb from various organs through chelation, but also saved the organs from oxidative damage. Thus, the C-Mn O NPs could be an effective nanotherapeutic agent for complete reversal of heavy-metal-induced toxicity through chelation of the heavy metal and healing of the associated oxidative stress.
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http://dx.doi.org/10.1002/cmdc.201900543DOI Listing
March 2020

Regulation of monoamine oxidase A (MAO-A) expression, activity, and function in IL-13-stimulated monocytes and A549 lung carcinoma cells.

J Biol Chem 2018 09 18;293(36):14040-14064. Epub 2018 Jul 18.

From the Department of Biotechnology, National Institute of Technology-Durgapur, Mahatma Gandhi Avenue, Durgapur-713209, Burdwan, West Bengal, India,

Monoamine oxidase A (MAO-A) is a mitochondrial flavoenzyme implicated in the pathogenesis of atherosclerosis and inflammation and also in many neurological disorders. MAO-A also has been reported as a potential therapeutic target in prostate cancer. However, the regulatory mechanisms controlling cytokine-induced MAO-A expression in immune or cancer cells remain to be identified. Here, we show that MAO-A expression is co-induced with 15-lipoxygenase (15-LO) in interleukin 13 (IL-13)-activated primary human monocytes and A549 non-small cell lung carcinoma cells. We present evidence that gene expression and activity are regulated by signal transducer and activator of transcription 1, 3, and 6 (STAT1, STAT3, and STAT6), early growth response 1 (EGR1), and cAMP-responsive element-binding protein (CREB), the same transcription factors that control IL-13-dependent 15-LO expression. We further established that in both primary monocytes and in A549 cells, IL-13-stimulated MAO-A expression, activity, and function are directly governed by 15-LO. In contrast, IL-13-driven expression and activity of MAO-A was 15-LO-independent in U937 promonocytic cells. Furthermore, we demonstrate that the 15-LO-dependent transcriptional regulation of MAO-A in response to IL-13 stimulation in monocytes and in A549 cells is mediated by peroxisome proliferator-activated receptor γ (PPARγ) and that signal transducer and activator of transcription 6 (STAT6) plays a crucial role in facilitating the transcriptional activity of PPARγ. We further report that the IL-13-STAT6-15-LO-PPARγ axis is critical for MAO-A expression, activity, and function, including migration and reactive oxygen species generation. Altogether, these results have major implications for the resolution of inflammation and indicate that MAO-A may promote metastatic potential in lung cancer cells.
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http://dx.doi.org/10.1074/jbc.RA118.002321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130935PMC
September 2018

Impact of density of coating agent on antibacterial activity of silver nanoparticle impregnated plasma treated activated carbon.

J Environ Sci (China) 2018 May 30;67:136-144. Epub 2017 Aug 30.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India. Electronic address:

To use stabilized nanoparticles (NPs) in water as disinfectants over a very long period, the amount of coating agent (for NP stabilization) needs to be optimized. To this end, silver nanoparticles (Ag-NPs) with two different coating densities of tri-sodium citrate (12.05 and 46.17molecules/nm, respectively), yet of very similar particle size (29 and 27 nm, respectively) were synthesized. Both sets of citrate capped NPs were then separately impregnated on plasma treated activated carbon (AC), with similar Ag loading of 0.8 and 0.82wt.%, respectively. On passing contaminated water (containing 10 CFU Escherichia coli/mL of water) through a continuous flow-column packed with Ag/AC, zero cell concentration was achieved in 22 and 39 min, with Ag-NPs (impregnated on AC, named as Ag/AC) having lower and higher coating density, respectively. Therefore, even on ensuring similar Ag-NP size and loading, there is a significant difference in antibacterial performance based on citrate coating density in Ag/AC. This is observed in lower coating density case, due to both: (i) higher Ag ion release from Ag-NP and (ii) stronger binding of individual Ag-NPs on AC. The latter ensures that, Ag-NP does not detach from the AC surface for a long duration. TGA-DSC shows that Ag-NPs with a low coating density bind to AC with 4.55 times higher adsorption energy, compared to Ag/AC with a high coating density, implying stronger binding. Therefore, coating density is an important parameter for achieving higher antibacterial efficacy, translating into a faster decontamination rate in experiments, over a long period of flow-column operation.
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http://dx.doi.org/10.1016/j.jes.2017.08.008DOI Listing
May 2018

Biofouling prevention using silver nanoparticle impregnated polyethersulfone (PES) membrane: E. coli cell-killing in a continuous cross-flow membrane module.

J Colloid Interface Sci 2017 Apr 17;491:13-26. Epub 2016 Nov 17.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India. Electronic address:

Biofouling significantly decreases membrane performance. So silver nanoparticle (Ag-NP) was impregnated selectively on a sulfonated polyethersulfone (SPES) membrane and its efficacy was tested in a continuous, cross-flow membrane module. The main challenges are: (i) to prevent biofouling on the membrane surface, (ii) achieve zero bacterial cell (E. coli) count in the permeate water, (iii) maintain Ag concentration in the permeate stream within the permissible limit of drinking water and (iv) maintain a high tensile strength of the membrane to prevent mechanical failure. Addressing these factors would ensure a long and productive service-life of the membrane. To this end, 10CFU/ml of E. coli cell-suspension was passed through the Ag-SPES membrane of 150μm total thickness, which has a narrow (1.74μm thickness), upper surface of Ag-NPs. We achieved zero E. coli cell-count and a minimum (10μg/L) Ag concentration in the permeate stream; simultaneously increasing the tensile strength from 2.78MPa to 3.92MPa due to Ag-NP impregnation. Thus, for a continuous inlet flow of E. coli contaminated water, the membrane module could deliver an almost constant permeate flow rate of 3.45L per hour, due to complete E. coli cell-killing. Simultaneously, Ag concentration in permeate stream is well-below the WHO's recommended limit of 100μg/L, for potable quality water. Therefore, the Ag-SPES membrane can be used as an anti-biofouling membrane in a continuous operational mode.
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http://dx.doi.org/10.1016/j.jcis.2016.11.060DOI Listing
April 2017

Water disinfection using silver nanoparticle impregnated activated carbon: Escherichia coli cell-killing in batch and continuous packed column operation over a long duration.

Water Res 2016 09 21;100:105-115. Epub 2016 Apr 21.

Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India. Electronic address:

Silver nanoparticles (Ag-NP) were selectively impregnated on the external surface of plasma treated activated carbon (AC) granules (referred to as Ag-AC hybrid, having 0.8 wt% of Ag), for achieving continuous disinfection of water in a single flow-column set-up. First, Ag-NPs (28 nm mean size) were synthesized by UV reduction. Subsequently, Escherichia coli cell-killing experiments were performed in both shake flask (i. e. batch-mode) and flow-column (i. e. continuous-mode) operations, using E. coli K12 (MTCC 1302) as a model organism. Batch results using 8 mg Ag-AC hybrid/ml of cell suspension showed that, 10(4) CFU/ml of cells were killed within 25 min contact time, with cell concentration decaying exponentially in time. Maintaining almost the same contact time as in the batch experiments, three columns packed with Ag-AC (all having a height of 25 cm but increasing diameters of 1, 5 and 8 cm, respectively) were used for monitoring cell-killing performance over a long duration. For all columns, inlet water having 10(4) CFU/ml E. coli could be completely disinfected to produce treated, outlet water having zero cell count. Specifically for the 8 cm diameter column, a maximum throughput of treating 1.62 L of contaminated water per hour could be maintained for at least up to 16 days. Moreover, the Ag concentration in the outlet water was only up to 29.8 μg/L at steady state, which is well within the recommended limit of 100 μg/L for drinking water. Hence, water disinfection for potable quality water (zero E. coli count and <100 μg/L Ag) can be achieved in a continuous manner over a long duration, with our packed Ag-AC column.
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http://dx.doi.org/10.1016/j.watres.2016.04.048DOI Listing
September 2016

A one-pot three-component reaction involving 2-aminochromone in aqueous micellar medium: a green synthesis of hexahydrochromeno[2,3-b]quinolinedione.

Mol Divers 2015 Aug 11;19(3):541-9. Epub 2015 Mar 11.

Department of Chemistry, R. K. Mission Vivekananda Centenary College, Rahara, Kolkata, 700118, West Bengal, India.

An efficient and green synthesis of hitherto unreported 11-(chromen-3-yl)-8,8-dimethyl-8,9-dihydro-6H-chromeno[2,3-b]quinoline-10,12(7H,11H)-dione has been accomplished by a three-component reaction involving 2-aminochromone, chromone-3-carbaldehyde, and 5,5-dimethyl-1,3-cyclohexanedione (dimedone) in 0.5 M aqueous SDS solution. The mechanism of the reaction has been studied by isolating the reaction intermediate. This methodology features eco-friendly reaction conditions, a simple working procedure, high atom-economy and high efficiency in product formation.
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http://dx.doi.org/10.1007/s11030-015-9573-7DOI Listing
August 2015