Publications by authors named "Raghumani S Ningthoujam"

7 Publications

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Hypoxia-responsive nanoparticle based drug delivery systems in cancer therapy: An up-to-date review.

J Control Release 2020 03 24;319:135-156. Epub 2019 Dec 24.

Chemistry Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.

Hypoxia is a salient feature observed in most solid malignancies that holds a pivotal role in angiogenesis, metastasis and resistance to conventional cancer therapeutic approaches, and thus enables cancer progression. However, the typical characteristics of hypoxic cells such as low oxygen levels and highly bio-reductive environment can offer stimuli-responsive drug release to aid in tumor-specific chemo, radio, photodyanamic and sonodynamic therapies. This approach based on targeting the poorly oxygenated tumor habitats offers the prospective to overcome the difficulties that arises due to heterogenic nature of tumor and could be possibly used in the design of diagnostic as well as therapeutic nanocarriers for targeting various types of solid cancers. Consequently, hypoxia triggered nanoparticle based drug delivery systems is a rapidly progressing research area in developing effective strategies to combat drug-resistance in solid tumors. The present review presents the recent advances in the development of hypoxia-responsive nanovehicles for drug delivery to heterogeneous tumors. The initial sections of the article provides insights into the development of hypoxia in growing cancer and its role in disease progression. The current limitations and the future prospective of hypoxia-stimulated nanomachines for cancer treatment are also discussed.
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http://dx.doi.org/10.1016/j.jconrel.2019.12.041DOI Listing
March 2020

Naphthalimides in fluorescent imaging of tumor hypoxia - An up-to-date review.

Bioorg Chem 2019 07 8;88:102979. Epub 2019 May 8.

Chemistry Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.

Hypoxia is a distinctive characteristic of advanced solid malignancies that results from a disparity between oxygen supply and its consumption. The degree of hypoxia is believed to have adverse prognostic significance. Therefore detecting cellular hypoxia can potentially offer insights into the grade of tumour as well as its evolution towards a progressive malignant phenotype, which clinically translates to greater metastatic potential and treatment resistance. Fluorescence imaging to visualize hypoxia in biological systems is a minimally-invasive method. Recently there are several reports on interdisciplinary research that aims at developing functional probes that can be efficiently used for non-invasive imaging of hypoxic tumours. Upregulated levels of nitroreductase (NTR) is detected in hypoxic solid malignancies, and this characteristic feature is increasingly utilized in the development of NTR-targeted fluorescent molecules to selectively sense hypoxia in vivo. The present review summarizes various reports published on the design concepts of nitro naphthalimide-based bio-reductive fluorescent sensors that can be applied noninvasively to image hypoxia in cancer.
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http://dx.doi.org/10.1016/j.bioorg.2019.102979DOI Listing
July 2019

Azodyes as markers for tumor hypoxia imaging and therapy: An up-to-date review.

Chem Biol Interact 2019 Jul 30;307:91-104. Epub 2019 Apr 30.

Department of Chemistry, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, 576 104, Karnataka, India.

Tumor hypoxia is the low tissue oxygen levels seen characteristically in rapidly proliferating and expanding neoplasms. It affects both malignant tumor cells and its microenvironment, resulting in dysfunctional neovascularization. This leads to epithelial-to-mesenchymal transition phenotype, facilitating tumor progression through cell mobility, invasion, and metastasis. The hypoxic condition in solid tumors is thus an indicator of the process of cancer progression towards an aggressive malignant phenotype with an enhanced possibility of metastasis and resistance to treatment. Advancements in the detection of tumor hypoxia and its utilization as a treatment modality in solid tumors are highly imperative. The use of fluorescent probes is an evolving field for detecting hypoxic tumors in biological systems. The present review is an attempt to provide a contextual knowledge on the prominent role of tumor hypoxia in cancer progression and dissemination. The use of azodyes in detecting tumor hypoxia aiding in cancer diagnosis through fluorescence off-on imaging and azodye-based hypoxia selective pro-drugs for assisting cancer therapy are presented. The limitations of fluorescence based hypoxia imaging and further investigations desired for clinical usage of azodye based hypoxic probes for fluorescence imaging are also considered.
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http://dx.doi.org/10.1016/j.cbi.2019.04.034DOI Listing
July 2019

Microwave Absorption and the Magnetic Hyperthermia Applications of LiZnCoFeO Nanoparticles in Multiwalled Carbon Nanotube Matrix.

ACS Appl Mater Interfaces 2017 Nov 13;9(46):40831-40845. Epub 2017 Nov 13.

Solid State Research Laboratory, Department of Physics, Burdwan University , Burdwan 713104, West Bengal, India.

Nanoparticles of LiZnCoFeO (LZC) were prepared by the sol-gel method and dried in a furnace at ∼200 °C. The dried sample was annealed at 500, 600, 700, and 800 °C for 5 h each. Rietveld analysis of X-ray diffraction patterns confirms the cubic Fd3̅m phase formation with lattice parameters ranged from 8.376 up to 8.390 Å and allows the crystallite sizes (d) to be estimated. To enhance microwave (MW) absorption as well as the effectiveness for hyperthermia treatment, nanoparticles are taken in the matrix of multiwalled carbon nanotubes (MWCNTs) and the morphology of the so-prepared samples ([email protected]) was studied by scanning electron microscopy and transmission electron microscopy analyses. Both static and dynamic magnetic properties were investigated on the samples of LZC nanoparticles and compared to those of the samples of [email protected] The samples annealed at 500, 600, and 800 °C are excellent candidates in cancer treatment as ac magnetic heating analysis shows that the hyperthermia temperature (42 °C) was successfully achieved for an applied ac magnetic field of 420 Oe and 300 kHz frequency. MW absorption study also reveals that the samples of [email protected] could be used as a potential MW absorbing material for which a maximum reflection loss (R) of ∼-21 dB was achieved at a frequency of 15.27 GHz for only 1 mm layer thickness.
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http://dx.doi.org/10.1021/acsami.7b12091DOI Listing
November 2017

Cellular and spectroscopic characterization of cancer stem cell-like cells derived from A549 lung carcinoma.

J Cancer Res Ther 2016 Jul-Sep;12(3):1144-1152

Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, Maharashtra, India.

Background: Cancer stem cells (CSCs) are increasingly being realized to play a significant role in the mechanism of chemo-, radio-resistance, and metastasis of cancer. However, studies for spectral markers of CSCs using Fourier transform infrared (FT-IR) and circular dichroism (CD) spectroscopy are limited in the literature.

Materials And Methods: In the present study, CSCs obtained from single cell assay of human lung adenocarcinoma (A549) cells were characterized using CD44+/CD24-/low phenotype expression, Hoechst 33342 dye efflux assay, and expression of stemness genes. Spectral changes in cancer cells and clones enriched with CSCs were studied by FT-IR and CD spectroscopy.

Results: The changes in FT-IR spectra of clones enriched with CSCs showed the difference in the secondary protein structure as compared to nonstem cancer cells. Moreover, A549 clone cells showed higher C-O band of carbohydrates and deoxyribose ring vibrations of Z-form of DNA. These results were further corroborated with CD spectroscopy that showed increased alpha helix proteins and difference in DNA conformation in clones enriched with CSCs. FT-IR studies also showed higher imidazole-metal interactions in clones enriched with CSCs. These results are in agreement with higher activity of one of the metalloproteins that is, superoxide dismutase in clones enriched with CSCs and their increased radioresistance.

Conclusions And General Significance: Overall, these observations provide novel FT-IR and CD spectroscopy signatures in A549 clones enriched with CSCs, which may have implications in the quantifying magnitude of CSCs as prognostic markers in cancer therapy.
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http://dx.doi.org/10.4103/0973-1482.171365DOI Listing
March 2017

The interaction of actinide and lanthanide ions with hemoglobin and its relevance to human and environmental toxicology.

J Hazard Mater 2016 Apr 29;307:281-93. Epub 2015 Dec 29.

Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.

Due to increasing use of lanthanides/actinides in nuclear and civil applications, understanding the impact of these metal ions on human health and environment is a growing concern. Hemoglobin (Hb), which occurs in all the kingdom of living organism, is the most abundant protein in human blood. In present study, effect of lanthanides and actinides [thorium: Th(IV), uranium: U(VI), lanthanum: La(III), cerium: Ce(III) and (IV)] on the structure and function of Hb has been investigated. Results showed that these metal ions, except Ce(IV) interacted with carbonyl and amide groups of Hb, which resulted in the loss of its alpha-helix conformation. However, beyond 75μM, these ions affected heme moiety. Metal-heme interaction was found to affect oxygen-binding of Hb, which seems to be governed by their closeness with the charge-to-ionic-radius ratio of iron(III). Consistently, Ce(IV) being closest to iron(III), exhibited a greater effect on heme. Binding constant and binding stoichiometry of Th(IV) were higher than that of U(VI). Experiments using aquatic midge Chironomus (possessing human homologous Hb) and human blood, further validated metal-Hb interaction and associated toxicity. Thus, present study provides a biochemical basis to understand the actinide/lanthanide-induced interference in heme, which may have significant implications for the medical and environmental management of lanthanides/actinides toxicity.
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http://dx.doi.org/10.1016/j.jhazmat.2015.12.029DOI Listing
April 2016

Surface chemistry of surfactant AOT-stabilized SnO(2) nanoparticles and effect of temperature.

J Colloid Interface Sci 2010 Sep 16;349(1):27-33. Epub 2010 May 16.

Department of Chemistry, Manipur University, Imphal 795003, India.

SnO(2).xH(2)O nanoparticles were prepared at room temperature by the microemulsion route. Sodium bis(2-ethylhexyl) sulfosuccinate (AOT) was used as a surfactant to stabilize the nanoparticles. These nanoparticles show green luminescence at 510nm, which has been assigned to oxygen vacancies. Infrared spectra of samples heated in the temperature range 500-900 degrees C show bond formation between SnO(2) nanoparticles and SO(4)(2-), which arises from oxidation of SO(3)(-) present in AOT. This was further supported by X-ray diffraction. Shape transformations of the particles from triangular to spherical and then to rectangular was observed as the heat-treatment temperature was increased, and this is related to the surface energy of particles. An enhancement in emission intensity of Eu(3+) was observed when Eu(3+) ions were doped into the SnO(2) nanoparticles due to significant energy transfer from SnO(2) (or Eu-O) to Eu(3+) through surface-mediated energy transfer as compared to direct excitation of Eu(3+) at 397nm. Interestingly, these nanoparticles are dispersible in water, and can be incorporated into polymer-based materials such as polyvinyl alcohol to give homogeneous films, giving rise to blue and red emissions.
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http://dx.doi.org/10.1016/j.jcis.2010.05.037DOI Listing
September 2010