Browsing by Author "Minakshi Prasad"

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Metal/metal oxide nanoparticles: Toxicity concerns associated with their physical state and remediation for biomedical applications
(Elsevier Inc., 2021) Anju Manuja; Balvinder Kumar; Rajesh Kumar; Dharvi Chhabra; Mayukh Ghosh; Mayank Manuja; Basanti Brar; Yash Pal; B.N. Tripathi; Minakshi Prasad
Metal/metal oxide nanoparticles show promise for various applications, including diagnosis, treatment, theranostics, sensors, cosmetics, etc. Their altered chemical, optical, magnetic, and structural properties have differential toxicity profiles. Depending upon their physical state, these NPs can also change their properties due to alteration in pH, interaction with proteins, lipids, blood cells, and genetic material. Metallic nanomaterials (comprised of a single metal element) tend to be relatively stable and do not readily undergo dissolution. Contrarily, metal oxide and metal alloy-based nanomaterials tend to exhibit a lower degree of stability and are more susceptible to dissolution and ion release when introduced to a biological milieu, leading to reactive oxygen species production and oxidative stress to cells. Since NPs have considerable mobility in various biological tissues, the investigation related to their adverse effects is a critical issue and required to be appropriately addressed before their biomedical applications. Short and long-term toxicity assessment of metal/metal oxide nanoparticles or their nano-formulations is of paramount importance to ensure the global biome's safety; otherwise, to face a fiasco. This article provides a comprehensive introspection regarding the effects of metal/metal oxides’ physical state, their surface properties, the possible mechanism of actions along with the potential future strategy for remediation of their toxic effects. © 2021 The Author(s)
Nanotechnology in Cancer Diagnosis and Therapy
(Springer Singapore, 2022) Minakshi Prasad; Lukumoni Buragohain; Mayukh Ghosh; Rajesh Kumar
Earliest precise diagnosis and targeted therapy underlines the efficiency of successful cancer management. Conventional diagnostics are usually dependent on phenotypic expression of cancer signatures which often effects into delayed detection leading to poor prognosis. Traditional therapeutics frequently lacks precise targeting leading to sub-optimal drug concentration as well as off-target systemic side effects. Nano-intervention delivers in both the aspects: integration of advanced imaging modalities with site-specific targeting of nano-imaging agents can improve the sensitivity and specificity of cancer detection along with advent of diverse nanoparticle-based biosensors extends the scope for rapid and point-of-care diagnosis. Moreover, multifunctional nanoparticles facilitate simultaneous diagnosis and therapies of cancers in one go. Nanoparticle-based drug delivery systems with spatio-temporally controlled release mechanism facilitate targeted payload conveyance at the tumor sites with prolongs maintenance of adequate drug concentration to curtail general toxicity of the chemotherapeutics. Furthermore, it augments the pharmacokinetic properties of the drugs by improving the penetration, distribution and bioavailability of the therapeutic agents, even occasionally fortifying with synergistic effects. Premature drug release, fast enzymatic degradation, and rapid clearance can also be avoided by exploiting nano-encapsulation and stimuli-responsive nanoparticle-based drug delivery systems. Cancer immunotherapy has also gained significant attention in current scenario which mostly relies upon nanoparticle-based biological and vaccine delivery systems along with introduction of nano-adjuvants as component of nano-vaccines to enhance the immunogenicity and protection against cancers. Thus nanotechnology has the potential to empower the arsenal against cancer by diverse means; however, it faces some inherent challenges such as potential toxicity of nanomaterials, stringent regulatory issues delaying smooth and timely clinical transition of nano-drugs, lack of established international standards and protocols, redundant nanoparticle applications, and associated issues regarding the intellectual property rights, etc. Diligent focused efforts from all the stakeholders globally is paying-off as significant improvement have been observed in the “bench to beside” transition of the nano-formulations and newer candidates are reaching the market at regular basis currently which ensures a bright future prospect of nanotechnology in cancer arena. © Springer Nature Singapore Pte Ltd. 2022.
Organoid Technology: A Reliable Developmental Biology Tool for Organ-Specific Nanotoxicity Evaluation
(Frontiers Media S.A., 2021) Minakshi Prasad; Rajesh Kumar; Lukumoni Buragohain; Ankur Kumari; Mayukh Ghosh
Engineered nanomaterials are bestowed with certain inherent physicochemical properties unlike their parent materials, rendering them suitable for the multifaceted needs of state-of-the-art biomedical, and pharmaceutical applications. The log-phase development of nano-science along with improved “bench to beside” conversion carries an enhanced probability of human exposure with numerous nanoparticles. Thus, toxicity assessment of these novel nanoscale materials holds a key to ensuring the safety aspects or else the global biome will certainly face a debacle. The toxicity may span from health hazards due to direct exposure to indirect means through food chain contamination or environmental pollution, even causing genotoxicity. Multiple ways of nanotoxicity evaluation include several in vitro and in vivo methods, with in vitro methods occupying the bulk of the “experimental space.” The underlying reason may be multiple, but ethical constraints in in vivo animal experiments are a significant one. Two-dimensional (2D) monoculture is undoubtedly the most exploited in vitro method providing advantages in terms of cost-effectiveness, high throughput, and reproducibility. However, it often fails to mimic a tissue or organ which possesses a defined three-dimensional structure (3D) along with intercellular communication machinery. Instead, microtissues such as spheroids or organoids having a precise 3D architecture and proximate in vivo tissue-like behavior can provide a more realistic evaluation than 2D monocultures. Recent developments in microfluidics and bioreactor-based organoid synthesis have eased the difficulties to prosper nano-toxicological analysis in organoid models surpassing the obstacle of ethical issues. The present review will enlighten applications of organoids in nanotoxicological evaluation, their advantages, and prospects toward securing commonplace nano-interventions. © Copyright © 2021 Prasad, Kumar, Buragohain, Kumari and Ghosh.
Proteomics and Metabolomics in Cancer Diagnosis and Therapy
(Springer Singapore, 2022) Minakshi Prasad; Somesh Banerjee; Suman; Rajesh Kumar; Lukumoni Buragohain; Mayukh Ghosh
Cancer apparently seems to be incurable but a deeper introspection reveals other story. Cancer survival rate can be increased significantly with early detection and proper therapeutic intervention. It can be vividly justified by the fact that breast cancer survival rates in high-income countries have reached over 80% while it is nearly 50% or even below in poorer countries. The reason for such contrasting picture can be understood as effective therapeutic facilities are available in above 90% of the developed countries as compared to treatment availability in below 30% of poorer countries. Proper diagnostic facilities are also lacking as only 26% of poorer countries can offer public sector pathology services according to 2017 WHO data. Conventional diagnostic approaches usually rely up on the clinical manifestation of aberration symptoms for disease diagnosis which is associated with significant delay in onset of therapeutic intervention. This is fatal, particularly for cancer as it urges earliest detection, preferably before metastasis for effective treatment outcome. State-of-the-art high-throughput proteomics and metabolomics techniques can offer solution as they identify the disease-associated molecular signatures much earlier than the traditional methods. Further, high resolution, single-cell or even organelle level penetration, extreme sensitivity, considerable reliability, and automation render them as potential platforms for identification of novel therapeutic targets as well which can facilitate development of extremely precise target-specific drugs to overcome the systemic side effects of traditional cancer chemotherapeutics. Separation-based chromatographic and electrophoretic methods such as liquid or gas chromatography (LC/GC) or capillary electrophoresis (CE) coupled with mass spectrometry (MS), Fluorescence-based methods, Raman-based methods, nuclear magnetic resonance (NMR), direct mass spectrometry imaging (MSI) are the mainstay of currently available proteomics and metabolomics analytical platforms. Although the spatiotemporal analyte dynamicity; generation, handling, and meaningful interpretation of the large data in biological context; dearth of universal standardized analytical protocols and specialized databases are posing limitations but continuous efforts from several stakeholders throughout the world is progressively alleviating the hurdles for transition of these high-end techniques from research arena to the field of routine clinical cancer diagnosis and therapy. Relentless progress in sample handling methods, instrumentation, computational software and data analyses programs ensure intense prospect of the techniques in oncology arena. © Springer Nature Singapore Pte Ltd. 2022.
Proteomics and Metabolomics in Cancer Diagnosis and Therapy
(Springer Nature, 2022) Minakshi Prasad; Somesh Banerjee; Suman; Rajesh Kumar; Lukumoni Buragohain; Mayukh Ghosh
Cancer apparently seems to be incurable but a deeper introspection reveals other story. Cancer survival rate can be increased significantly with early detection and proper therapeutic intervention. It can be vividly justified by the fact that breast cancer survival rates in high income countries have reached over 80% while it is nearly 50% or even below in poorer countries. The reason for such contrasting picture can be understood as effective therapeutic facilities are available in above 90% of the developed countries as compared to treatment availability in below 30% of poorer countries. Proper diagnostic facilities are also lacking as only 26% of poorer countries can offer public sector pathology services according to 2017 WHO data. Conventional diagnostic approaches usually rely up on the clinical manifestation of aberration symptoms for disease diagnosis which is associated with significant delay in onset of therapeutic intervention. This is fatal, particularly for cancer as it urges earliest detection, preferably before metastasis for effective treatment outcome. State-of-the-art high-throughput proteomics and metabolomics techniques can offer solution as they identify the disease associated molecular signatures much earlier than the traditional methods. Further, high resolution, single-cell or even organelle level penetration, extreme sensitivity, considerable reliability, and automation render them as potential platforms for identification of novel therapeutic targets as well which can facilitate development of extremely precise target-specific drugs to overcome the systemic side-effects of traditional cancer chemotherapeutics. Separation based chromatographic and electrophoretic methods such as liquid or gas chromatography (LC/GC) or capillary electrophoresis (CE) coupled with mass spectrometry (MS), fluorescence-based methods, Raman-based methods, nuclear magnetic resonance (NMR), direct mass spectrometry imaging (MSI) are the mainstay of currently available proteomics and metabolomics analytical platforms. Although the spatiotemporal analyte dynamicity; generation, handling, and meaningful interpretation of the large data in biological context; dearth of universal standardized analytical protocols and specialized databases are posing limitations, continuous efforts from several stakeholders throughout the world are progressively alleviating the hurdles for transition of these high-end techniques from research arena to the field of routine clinical cancer diagnosis and therapy. Relentless progress in sample handling methods, instrumentation, computational software, and data analyses programs ensure intense prospect of the techniques in oncology arena. © Springer Nature Singapore Pte Ltd. 2022.
Single cell metabolomics
(Elsevier, 2022) Minakshi Prasad; Mayukh Ghosh; Rajesh Kumar
Single-cell techniques are evolving rapidly to capture the stimuli-responsive deterministic variations occurring at the cellular and subcellular level, precisely targeting the heterogeneity of spatiotemporal analyte expression arising from divergent cellular phenotypes. Single-cell metabolomics (SCM) is relatively nascent than the other single-cell techniques such as single-cell sequencing and single-cell proteomics; yet, the potential of SCM has already been perceived through diverse biological applications including but not limited to microbial technology, plant science and agriculture, developmental biology, aging and senescence study, stem cell biology, functional genomics, nutrition research, environmental biology, system biology, immunology, drug discovery and toxicity analyses, disease diagnosis and therapy, etc. Currently, bulk of the SCM research has been directed toward the establishment and validation of the newer SCM analytical modalities along with proof-of-concept interventions. Now, time has come to channelize the efforts toward improving the frequency of “bench to beside” transition of these state-of-the-art SCM techniques for commonplace biological applications from the on-going status of typically specialized interventions. Standardization of SCM procedures and customization of general SCM workflow compatible with broader samples and analytes, strengthening of SCM database, facilitation of data sharing option from different analytical platforms and among diverse scientific beneficiaries, integration of multiple single-cell intervention outcomes to generate reliable models for diagnostic and therapeutic intervention, etc. are certain measures that can improve the on-field transition of SCM interventions for diverse biological applications. © 2022 Elsevier Inc. All rights reserved.
Single Cell Metabolomics: A Future Tool to Unmask Cellular Heterogeneity and Virus-Host Interaction in Context of Emerging Viral Diseases
(Frontiers Media S.A., 2020) Rajesh Kumar; Mayukh Ghosh; Sandeep Kumar; Minakshi Prasad
Viral emergence is an unpredictable but obvious event, particularly in the era of climate change and globalization. Efficient management of viral outbreaks depends on pre-existing knowledge and alertness. The potential hotspots of viral emergence often remain neglected and the information related to them is insufficient, particularly for emerging viruses. Viral replication and transmission rely upon usurping the host metabolic machineries. So altered host metabolic pathways can be exploited for containment of these viruses. Metabolomics provides the insight for tracing out such checkpoints. Consequently introspection of metabolic alteration at virus-host interface has evolved as prime area in current virology research. Chromatographic separation followed by mass spectrometry has been used as the predominant analytical platform in bulk of the analyses followed by nuclear magnetic resonance (NMR) and fluorescence based techniques. Although valuable information regarding viral replication and modulation of host metabolic pathways have been extracted but ambiguity often superseded the real events due to population effect over the infected cells. Exploration of cellular heterogeneity and differentiation of infected cells from the nearby healthy ones has become essential. Single cell metabolomics (SCM) emerges as necessity to explore such minute details. Mass spectrometry imaging (MSI) coupled with several soft ionization techniques such as electrospray ionization (ESI), laser ablation electrospray ionization (LAESI), matrix assisted laser desorption/ionization (MALDI), matrix-free laser desorption ionization (LDI) have evolved as the best suited platforms for SCM analyses. The potential of SCM has already been exploited to resolve several biological conundrums. Thus SCM is knocking at the door of virus-host interface. © Copyright © 2020 Kumar, Ghosh, Kumar and Prasad.
Wnt Signaling in Cancer
(Springer Nature, 2022) Minakshi Prasad; Mayukh Ghosh; Rajesh Kumar; Lukumoni Buragohain; Ankur Kumari; Gaya Prasad
Stringent regulation of the Wnt pathways components and modulators is indispensable for the restoration of tissue homeostasis and development. The Wnt/β-catenin-dependent canonical pathway is the most comprehensively introspected Wnt signaling pathway which relies upon Frizzled receptor activation and cytosolic β-catenin stabilization followed by their nuclear transport and subsequent transcriptional activation of multiple target genes to influence multiple cellular processes. The β-catenin-independent noncanonical pathway is the alternative Wnt signaling pathway which operates through either planar cell polarity [PCP] or calcium-signaling mechanism to modulate gene regulation. These pathways are highly branched and interconnected to modulate downstream mechanisms individually or in a concerted fashion. Aberrant Wnt signaling induced by genetic or epigenetic impetus leads to carcinogenesis and metastasis; evidently, several cancer types have depicted alterations in multiple Wnt pathway components to render them as potential targets for anticancer chemotherapy. Several small molecules and biologicals antagonizing the Wnt signaling are currently undergoing through different stages of clinical trial for customizing efficacious as well as safe anticancer therapeutics. However, the healthy cells are also susceptible to blockage of Wnt signaling pathways as potential side effects that pose inherent challenge to the strategy which needs to be dealt with utmost precaution. Cancer-specific Wnt markers and combination of multiple therapeutic strategies can overcome the limitation which lies at the focus of the ongoing oncotherapeutic introspections. © Springer Nature Singapore Pte Ltd. 2022.