Browsing by Author "Partha Pratim Manna"

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A 1,8 naphthalimide anchor rhodamine B based FRET probe for ratiometric detection of Cr3+ion in living cells
(Elsevier B.V., 2019) Susanta Adhikari; Sabyasachi Ta; Avijit Ghosh; Subhajit Guria; Abhishek Pal; Manisha Ahir; Arghya Adhikary; Sumit Kumar Hira; Partha Pratim Manna; Debasis Das
A 2-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)acetaldehydeanchored rhodamine B based probe, RDNAP detects Cr3+ ion by fluorescence resonance energy transfer (FRET) process in aqueous buffered acetonitrile media (7:3, v/v). Conversely, conjugation of 2-(1,3-dioxo-6-(piperidin-1-yl)-1H-benzo[de]isoquinolin-2(3H)-yl)acetaldehyde with rhodamine B provides another probe, RDNAP-PY that undergoes Cr3+assisted ratiometric fluorescence and colorimetric change in the same media. RDNAP-PY provides higher FRET efficiency and detects as low as 1.81×10−6 M Cr3+with an association constant, 15.9 × 104 M−1. Other common ions do not interfere. RDNAP-PY efficiently images intracellular Cr3+ in live Hep3B, MCF-7, HeLa, SiHa and HEK 293T cells under fluorescence microscope in a ratiometric and time dependent manner. 1H NMR titration and DFT studies strongly support experimental findings. © 2018 Elsevier B.V.
A unique benzimidazole-naphthalene hybrid molecule for independent detection of Zn2+ and N3 − ions: Experimental and theoretical investigations
(Elsevier B.V., 2019) Sabyasachi Ta; Sudipta Das; Milan Ghosh; Mahuya Banerjee; Sumit Kumar Hira; Partha Pratim Manna; Debasis Das
Single crystal X-ray structurally characterized benzimidazole-naphthalene hybrid (NABI) functions as a unique dual analyte sensor that can detect Zn2+ cation and N3 − anion independently. The NABI forms chelate with Zn2+ to inhibit internal charge transfer (ICT) and –CH[dbnd]N– isomerisation resulting chelation enhanced fluorescence (CHEF). On the other hand, the sensing of N3 − is based on formation of supramolecular H-bonded rigid assembly. The association constant of NABI for Zn2+ and N3 − ions are 19 × 104 M−1 and 11 × 102 M−1, respectively. Corresponding limit of detections (LOD) are 6.85 × 10−8 and 1.82 × 10−7 M, respectively. NABI efficiently detects intracellular Zn2+ and N3 − ions with no cytotoxicity on J774A.1cells under fluorescence microscope. DFT studies unlock underlying spectroscopic properties of free NABI and Zn2+/N3 − bound forms. © 2018 Elsevier B.V.
Antiproliferative activity of Fe(ii), Co(ii), Ni(ii), Cu(ii), and Zn(ii) complexes of dithiocarbamate: synthesis, structural characterization, and thermal studies
(Royal Society of Chemistry, 2023) Anupam Singh; Kunal Shiv; Ranjeet Singh; M.K. Bharty; Partha Pratim Manna; Lal Bahadur Prasad
Five new metal complexes of Fe(ii) (1), Co(ii) (2), Ni(ii) (3), Cu(ii) (4), and Zn(ii) (5), derived from an N-cyclohexyl N-(3,4-dimethoxybenzyl) dithiocarbamate ligand, have been successfully synthesized and fully characterized by different analytical techniques i.e. elemental analyses, FT-IR, UV-Vis, 1H & 13C NMR, and HRMS. Furthermore, complexes 4 and 5 have been characterized by the SC-XRD technique. Complex 4 adopts a distorted square planar geometry around the Cu(ii) center while complex 5 adopts a distorted tetrahedral geometry around the Zn(ii) center. In addition, an eight-membered symmetric chair-like metallacycle ring containing two Zn(ii) centers has also been found in complex 5. XRD data also show that complexes 4 and 5 are stabilized by various weak intermolecular hydrogen bonding interactions. The course of the thermal degradation of metal complexes 1-5 has been examined by TG-DTA data which revealed that metal sulphide formed as the final residue. Complexes 1-5 demonstrated concentration-dependent cytotoxicity and growth inhibition of DL tumor cells. Among the compounds, complexes 1, 4, and 5 showed significant cytotoxicity and induced a loss in the viability of DL cells. Therapy with complexes 1, 4, and 5 protects DL tumor-bearing animals from exacerbation of the disease, increases lifespan, and significantly improves the histopathological parameters of the vascularized organ, including preventing metastasis. Overall cytotoxicity assay results indicate that all complexes have remarkable cytotoxic potential in comparison with the free ligand. © 2024 The Royal Society of Chemistry.
Aqua-(2-formylbenzoato)triphenyltin(IV) induces cell cycle arrest and apoptosis in hypoxic triple negative breast cancer cells
(Elsevier Ltd, 2023) Virendra Singh; Nishant Kumar Rana; Mohammad Kashif; Partha Pratim Manna; Tushar S. Basu Baul; Biplob Koch
Hypoxia plays a vital role in tumor microenvironment by allowing development and maintenance of cancer cells thereby led to major hindrance for effective anticancer therapy and main reason for failure of most anticancer drugs. We herein investigated the therapeutic efficacy and molecular mechanism of action of aqua-(2-formylbenzoato) triphenyltin (IV) compound (OTC) in MDA-MB-231 cell line. Cobalt chloride induced hypoxic MDA-MB-231 cells treated with OTC were used to access cytotoxicity, ROS, cellular apoptosis, and cell cycle progression. Further, expression of HIF-1α and VEGF, as well as apoptotic proteins like p53, Bax, Bcl-2 and caspase 3 were assessed. The findings indicated that OTC is more effective towards CoCl2 induced hypoxic cells when compared to normoxic cells and the results are far superior to doxorubicin. Additionally, our study revealed that OTC facilitates more ROS production induced cell cycle arrest and promote apoptosis. Furthermore, OTC significantly down regulates the expression of Hif-1α, VEGF and Bcl-2 in hypoxic condition and elevates the level of p53, Bax, cytochrome-C and Caspase 3. Our in vitro studies demonstrated that OTC showed better efficacy than doxorubicin, corroborating that OTC could be a promising compound for hypoxic cancer that also display multi drug resistant. © 2022 Elsevier Ltd
ATP-Decorated Mesoporous Silica for Biomineralization of Calcium Carbonate and P2 Purinergic Receptor-Mediated Antitumor Activity against Aggressive Lymphoma
(American Chemical Society, 2018) Prateek Srivastava; Sumit Kumar Hira; Divesh Narayan Srivastava; Vivek Kumar Singh; Uttam Gupta; Ranjeet Singh; Ram Adhar Singh; Partha Pratim Manna
Adenosine triphosphate (ATP) is an important transmitter that mediates various biological effects via purinergic receptors (P2 receptors) in cancer. We investigated the antitumor activity of ATP-decorated and doxorubicin (DOX)-loaded mesoporous silica with biomineralization of calcium carbonate against a highly aggressive and metastatic murine lymphoma called Dalton's lymphoma (DL). Our results suggest that this nanocomposite has unique effects with respect to the morphology and properties of calcium carbonate on the surface of the nanoparticle. DOX in the nanoparticles was prevented from quick release via the interactions of the phosphate group present on ATP and calcium carbonate. This construct is significantly tumoricidal against parental and DOX-resistant DL cells and is thus a promising candidate for applications in drug delivery. The composite nanomaterial has excellent biocompatibility with higher uptake and acts via the participation of the purinergic receptor P2X7. The nanocomposite induces significantly higher apoptosis in tumor cells compared with DOX alone. Treatment of DL-bearing mice with the construct significantly reduces tumor burden, in addition to augmenting the lifespan of tumor-bearing mice as demonstrated by a sustained healthy life of the animals and improved histopathological parameters. © 2018 American Chemical Society.
Biocompatible thermoresponsive N-isopropyl-N-(3-(isopropylamino)-3-oxopropyl)acrylamide-based random copolymer: synthesis and studies of its composition dependent properties and anticancer drug delivery efficiency
(Royal Society of Chemistry, 2022) Sourov Mondal; Archana Kumari; Kheyanath Mitra; Abhineet Verma; Satyen Saha; Biswajit Maiti; Ranjeet Singh; Partha Pratim Manna; Pralay Maiti; Hironobu Watanabe; Masami Kamigaito; Biswajit Ray
A new acrylamide monomer, N-isopropyl-N-(3-(isopropylamino)-3-oxopropyl)acrylamide (M3i), consisting of both isopropyl and isopropylamidopropyl moieties, has been synthesized from isopropylamine and N-isopropylacrylamide via an aza-Michael addition reaction followed by amidation with acryloyl chloride. The homopolymer of M3i (polyM3i) and a series of random copolymers of M3i and poly(ethylene glycol)methyl ether acrylate (PEGA: CH2 00000000 00000000 00000000 00000000 11111111 00000000 11111111 00000000 00000000 00000000 CHCO2(CH2CH2O)nMe, Mn = 480, n = 9 on average) with varying compositions have been synthesized via reversible addition-fragmentation chain transfer polymerization using 2-(dodecylthiocarbonothioylthio)-2-methylpropionic acid (DDMAT) as well as 1-phenylethyl phenyl dithioacetate (PEPD) as a RAFT agent. These polymers have been characterized by 1H NMR, FTIR, GPC, UV-Vis, fluorescence, TGDTA, DSC, DLS, and TEM techniques. A lower critical solution temperature (LCST) and glass transition temperature (Tg) for polyM3i prepared using DDMAT were observed at 17 and 133 °C, respectively, while for a polymer formed using PEPD, no LCST was observed until 0 °C and its observed Tg was found at 127.3 °C. The polymers are thermally stable up to 300 °C. Upon an increase in the M3i content in the copolymers, LCST decreases, Tg increases, and the apparent hydrodynamic diameter decreases. Moreover, the effects of concentration and the addition of urea and sodium chloride on the LCST of the copolymer with an LCST close to body temperature were studied. Owing to the incorporation of PEGA, a higher critical micellar concentration and larger TEM particle size of this copolymer were observed with respect to those of polyM3i. The usefulness of the micelles of the copolymers as nano-carriers for the drug doxorubicin was explored. The in vitro tumoricidal activity of the micelles of the doxorubicin-loaded copolymers was also assessed against Dalton's lymphoma cells. © 2022 The Royal Society of Chemistry.
Brightening Quinolineimines by Al3+ and Subsequent Quenching by PPi/PA in Aqueous Medium: Synthesis, Crystal Structures, Binding Behavior, Theoretical and Cell Imaging Studies
(American Chemical Society, 2017) Sharad Kumar Asthana; Ajit Kumar; Neeraj; Shweta; Sumit Kumar Hira; Partha Pratim Manna; K.K. Upadhyay
Recent years have witnessed an upsurge of Al3+ selective optical sensors involving simple Schiff bases to other complex organic frameworks. However, more than ∼95% of such reports lack crystallographic evidence, and proposals of binding sites for Al3+ are based upon spectroscopic evidence only. We herein synthesized and fully characterized a quinolineimine derivative (CMO) and explored its potential toward efficient detection of Al3+ with crystallographic evidence. The ongoing nonradiative photoinduced electron transfer (PET) and excited state intramolecular proton transfer (ESIPT) processes in CMO got inhibited via the chelation enhanced fluorescence (CHEF) effects induced by Al3+, and consequently turn-on fluorescence response was observed with 18-fold emission enhancements. The theoretical calculations performed were in good consonance with experimental results. We also explored further the applicability of the CMO·Al3+ complex toward highly sensitive and selective detection of inorganic phosphate (PPi) and an explosive picric acid (PA) via fluorescence quenching processes through two different chemical routes. The bioimaging of Al3+ and PPi were carried out in the living human cancer cells (MCF-7). © 2017 American Chemical Society.
Cellular therapy by allogeneic macrophages against visceral leishmaniasis: Role of TNF-α
(Academic Press Inc., 2014) Partha Pratim Manna; Sumit Kumar Hira; Anirban Basu; Santu Bandyopadhyay
Tumor necrosis factor α (TNF-α) is an essential player in infection with Leishmania, controlling inflammatory lesion and parasite killing. We recently have shown the leishmanicidal activity of transmembrane form of TNF (mTNF) derived from allogeneic natural killer (NK) cells in experimental visceral leishmaniasis. Allogeneic macrophages and human monocytes derived mTNF has significantly higher antileishmanial activity compared to allogeneic NK cells. Unlike NK cells, syngeneic macrophages also possess antileishmanial activity, although degree of activity is significantly less compared to allogeneic macrophages. Cellular therapy by intravenous transfer of allogeneic macrophages enhances leishmanicidal effect against the established infection in susceptible animal by reducing the splenic parasite burden to 28.3±4.71×105 compared to 256.00±17.36×105 in control group. In vivo treatment with anti-mouse TNF-α reduces the therapeutic efficacy of the allogeneic macrophages by increasing the parasite load in spleen of infected mice. These results demonstrated that allogeneic and xenogeneic macrophages induce cytokine mediated protective mechanism against infected macrophages via TNF-α in vitro and, possibly in vivo. The macrophage mediated protective role in absence of T cell help demonstrate an unique property of the mononuclear phagocytes in controlling infection and inflammation in visceral leishmaniasis, despite being acts as a host cell for the same parasite. © 2014 Elsevier Inc.
Chemokine-targeted nanoparticles: stimulation of the immune system in cancer immunotherapy
(Open Exploration Publishing Inc, 2023) Ranjeet Singh; Prateek Srivastava; Partha Pratim Manna
Surgery, chemotherapy, radiation therapy, and immunotherapy are potential therapeutic choices for many malignant and metastatic cancers. Despite adverse side effects and pain, surgery and chemotherapy continue to be the most common cancer treatments. However, patients treated with immunotherapy had better cancer control than those who got other treatments. There are two methods to activate immunological pathways: systemically and locally. To modify the tumor microenvironment (TME), the former uses systemic cytokine/chemokine (CK) delivery, whilst the latter uses immunological checkpoints or small molecule inhibitors. Organic and inorganic nanomaterials (NMs) enhanced the efficacy of cancer immunotherapy. NMs can transmit drugs, peptides, antigens, antibodies, whole cell membranes, etc. Surface-modified NMs precisely target and enter the tissues. The inner core of surface-modified NMs is composed of chemicals with limited bioavailability and biocompatibility, resulting in prolonged blood retention and decreased renal clearance. These platforms hinder or prevent many immune cell activities and modify the TME, enhancing the efficiency of cancer immunotherapy. By inhibiting CK/CK receptor signaling, cell migration and other immune responses could be controlled. Developing CK-targeted nanoparticles (NPs) that inhibit CK signaling or take advantage of the ligand-receptor connection is possible. Surface chemical modification of NMs with CKs or specific peptides has several medicinal applications, including tissue-specific drug delivery and limited cell migration in cancer-afflicted conditions. This review covers current developments in the role of different groups of CK-loaded NP in tumor therapy targeting immune cells and cancer. It also covers the role of NP targeting CK signaling which aids in immunogenic cell death (ICD) and induction of antitumor immunity. In addition, CK gene silencing and its capacity to prevent cancer metastasis as well as inhibition of immune cell migration to modulate the TME are discussed. © The Author(s) 2023.
Detection of Hg 2+ ion using highly selective fluorescent chemosensor in real water sample and in-vitro cell study upon breast adenocarcinoma (MCF-7)
(Taylor and Francis Ltd., 2019) Swapan Dey; Ashish Kumar; Sumit Kumar Hira; Partha Pratim Manna
A novel rhodamine-based chemosensor (R) was designed and synthesised for selective recognition of Hg 2+ ion in real water samples collected from different places. The chemosensor was prepared in green condition with high yield. The selectivity of R was examined with various metal ions, among which only Hg 2+ was identified selectively with off–on mechanism along with enhancement of fluorescence. Metal ions recognition has been carried out using UV–vis and fluorescence studies taking µM concentration of chemosensor R in HEPES buffer. The detection limit of R was calculated and found to be 4.4 × 10 –9 M. Quantum chemical (DFT) calculation was carried out in order to acquire knowledge about the stability of R in presence of Hg 2+ ions. Cell viability and fluorescence microscopic experiments showed R as cytocompatible and can be used as a fluorescent probe for detecting Hg 2+ in living cells. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.
Development of a PAMAM Dendrimer for Sustained Release of Temozolomide against Experimental Murine Lymphoma: Assessment of Therapeutic Efficacy
(American Chemical Society, 2021) Ugir Hossain Sk; Sumit Kumar Hira; Abhinandan Rej; Debapriya Roymahapatra; Partha Pratim Manna
Enhanced drug localization at the tumor sites with minimal toxicity was demonstrated using dendrimer-conjugated temozolomide for treating experimental lymphoma, developed as a solid tumor. Herein, we have constructed a polyamidoamine (PAMAM) dendrimer conjugated with temozolomide to enhance the stability of the active drug metabolites, derived from the prodrug temozolomide. Our results suggest that the active drug (5-(3-methyltriazen-1-yl)imidazole-4-carboxamide) (MTIC) (derived from temozolomide) showed stable and sustained release from the dendrimer-temozolomide conjugate, suggesting the suitability of the construct for therapy. Besides growth inhibition and direct killing, the dendrimer-temozolomide construct induced extensive apoptosis not only in parental Dalton lymphoma tumor cells but also in the doxorubicin-resistant form of the tumor cells. Dendrimer-temozolomide conjugation significantly reduced the solid tumor growth and increased the lifespan with better prognosis, including improved histopathology of the treated mice, while untreated littermates developed extensive metastasis and succumbed to death. © 2021 American Chemical Society.
Development of a selective reaction-based turn-on fluorosensor and biomarker for hypochlorite ions in aqueous media
(Royal Society of Chemistry, 2019) Ejaj Ahmmed; Somenath Lohar; Sumanta Ghatak; Sumit Kumar Hira; Partha Pratim Manna; Pabitra Chattopadhyay
A new organic moiety, 2-benzotriazol-2-yl-6-[1,3]dithiolan-2-yl-4-ethyl-phenol (LH), was designed, synthesized and structurally characterized as an excellent sensor for hypochlorite ions in aqueous media at pH 7.4. The non-fluorescent LH showed outstanding ICT-based switch-on fluorescence for hypochlorite ions at a concentration as low as 12.58 nM with great sensitivity based on the hypochlorite ion-selective controlled oxidation cleavage reaction of its thioacetal linkage, which was supported by 1HNMR and 13CNMR titrations. The observed spectroscopic changes were validated by theoretical (DFT) calculations. The non-cytotoxic probe has potential application for hypochlorite (ClO-) ion imaging in living cells, which was revealed by imaging human breast cancer (MCF-7) and murine macrophage (J774A1) cell lines via fluorescence microscopy. © 2019 The Royal Society of Chemistry.
Down regulation of CD24 and HER-2/neu in breast carcinoma cells by activated human dendritic cell. Role of STAT3
(2012) Sumit Kumar Hira; Partha Pratim Manna
Human dendritic cells (DCs) stimulated with cytokines and LPS down regulate the expression of proto-oncogene HER-2/neu and GPI linked protein CD24 in breast cancer cell lines. We demonstrated that naïve DC from human peripheral blood, when stimulated with IFN-γ, IL-15 or LPS reduces the expression of HER-2/neu and CD24, via activation of TNF-α. Pretreatment of tumor cells with STAT3 specific inhibitors or knocking down of STAT3 by SiRNA makes the tumor cell more susceptible to apoptosis and DC mediated inhibition of both CD24 and HER-2/neu. Thus DC could acts as an inhibitory regulator in suppressing oncogene and prevention of metastasis. © 2012 Elsevier Inc.
Downregulation of endogenous STAT3 augments tumoricidal activity of interleukin 15 activated dendritic cell against lymphoma and leukemia via TRAIL
(Academic Press Inc., 2014) Sumit Kumar Hira; Indrani Mondal; Debasis Bhattacharya; Partha Pratim Manna
Effector functions in tumor resistance by dendritic cells (DCs) are less well characterized. In this study, we describe that the murine DCs upon stimulation with recombinant IL-15 in vitro or in vivo, expresses TNF superfamily member TRAIL which mediates cytotoxicity and growth inhibition against a murine lymphoma called Dalton lymphoma (DL) via apoptosis. Presence of tumor lysate or intact tumor cells significantly reduces the DC mediated tumoricidal effect, possibly via masking and down-regulating TRAIL in DCs. The antitumor effect of DC derived TRAIL was further augmented by deactivation of STAT3 in tumor cells by cucurbitacin I, which makes it more susceptible to DC derived TRAIL Treatment of tumor cells with cucurbitacin I upregulates TRAIL receptor expression in addition to activation of caspases. Compared to naïve DCs, DCs from tumor bearing mice are significantly impaired in TRAIL expression and consequent antitumor functions against DL which was partially restored by activation with IL-15 or LPS. Priming with recombinant IL-15 prolongs the survival of tumor bearing mice treated with cucurbitacin I. Naïve peripheral blood DCs derived from chronic myeloid leukemia (CML) patients have significant impairment in expression of TRAIL and consequent tumoricidal properties against TRAIL sensitive lymphoma cell lines and primary tumor cells compared to normal control. © 2014 Elsevier Inc.
Downregulation of STAT3 phosphorylation enhances tumoricidal effect of IL-15-activated dendritic cell against doxorubicin-resistant lymphoma and leukemia via TNF-α
(Elsevier Ltd, 2015) Sumit Kumar Hira; Indrani Mondal; Debasis Bhattacharya; Kailash Kumar Gupta; Partha Pratim Manna
Abstract Although disputed by some, increasing evidence suggests that TNF-α synergies with traditional chemotherapeutic drugs to exert a heightened antitumor effect. The present study investigated the antitumor efficacy of recombinant IL-15 in combination with the STAT3 inhibitor cucurbitacin-I in a doxorubicin-resistant murine lymphoma model. The significance of the work is to understand and design effective strategies in doxorubicin resistant lymphomas. TNF-α is downregulated in dendritic cells from mice with Dalton's lymphoma and shows an inverse relationship with disease progression. Doxorubicin-resistant DL cells have elevated levels of Bcl-2 and Mcl-1 and increased phosphorylation of STAT3. These cells are refractory to dendritic cell derived TNF-α. Doxorubicin resistant Dalton's lymphoma is susceptible to dendritic cell derived TNF-α upon stimulation with the STAT3 inhibitor cucurbitacin-I, which downregulates STAT3 and other survival molecules. The combined treatment of low dose of cucurbitacin-I and rIL-15 is ineffective in mice with doxorubicin resistant Dalton's lymphoma, but a similar therapy prolongs the survival of mice transplanted with parental Dalton's lymphoma. Doxorubicin resistant Dalton's lymphoma responds to therapy with high doses of cucurbitacin-I and rIL-15. Dendritic cell derived from mice responded positively to the therapy and regained their tumoricidal properties with respect to growth inhibition and killing of DL tumor cells. Similar to DL, DC derived from CML patients are impaired in TNF-α expression and are unable to restrict the growth of drug-resistant lymphoma and leukemia cells. This combination approach could be used as a new therapeutic strategy for aggressive and highly metastatic doxorubicin resistant lymphoma. © 2015 Elsevier Ltd.
Doxorubicin loaded pH responsive biodegradable ABA-type Amphiphilic PEG-b-aliphatic Polyketal-b-PEG block copolymer for therapy against aggressive murine lymphoma
(Elsevier Inc., 2020) Sumit Kumar Hira; Kheyanath Mitra; Prateek Srivastava; Shikha Singh; Sambhav Vishwakarma; Ranjeet Singh; Biswajit Ray; Partha Pratim Manna
A novel ABA-type polyethylene glycol (PEG)-b-polyketal (PK)-b-PEG block copolymer was synthesized via click reactions between the monoazido-monomethoxy-PEG and dialkyne terminated aliphatic polyketal with no carboxylic/amide linkages. Formation of the novel block copolymer was confirmed by 1H NMR, GPC, TGA, and DSC studies. The formed copolymer has shown faster degradation at acidic pH. Self-assembly of this block copolymer (average size 6.2 nm) was assessed by fluorescence study using pyrene as a probe. Doxorubicin loaded block copolymeric micelles (69.9 nm) have shown pH dependent elevated drug release at pH 6.4, indicating its potential as a pH responsive nano-carrier for anticancer therapy. The nano-sized copolymer demonstrated tumoricidal activities against the lymphoma of murine and human origin with significant levels of growth inhibition and apoptosis. Therapy with doxorubicin loaded copolymer reduced the tumor size and augmented the life span of the tumor bearing animals with improved histopathological parameters, compared with the untreated control. © 2019 Elsevier Inc.
Effector Functions of Dendritic Cells in Cancer: Role of Cytotoxicity and Growth Inhibition
(IMR Press Limited, 2024) Pratima Chaudhary; Prateek Srivastava; Partha Pratim Manna
The tumor microenvironment plays a critical role in modulating immune responses associated with tumorigenesis, tumor progression, and metastasis. Dendritic cells (DC) play a key role in preventing and progression of metastatic neoplasia by driving and restoring dysfunctional immune systems and obliterating immunosuppression, thus obstructing tumor evasion. In this review, we will discuss the functions of tumor-infiltrating DC in anti-tumor resistance, prevention of tumor recurrence, and immunosuppression. We will also describe DC metabolism, differentiation, and plasticity, which are essential for its function. Cancers like Lymphomas may be able to corrupt immune surveillance by reducing natural killer cell numbers. Thus, interactions between lymphoma and DC with reference to cytotoxicity may be an important event, likely to be mediated via activation with interferon-γ (IFN-γ) and Toll like receptors (TLR) ligands. Mechanisms of DC-mediated cytotoxicity and the role of apoptosis and death receptors, including the role played by nitric oxide, etc., are of immense significance. We will also look into the molecular mechanisms in the tumor microenvironment, reduced drug sensitivity, and tumor relapse, as well as methods for combating drug resistance and focusing on immunosuppressive tumor networks. We will address how DC mediated cytotoxicity in combination with drugs affects tumor growth and expansion in relation to checkpoint inhibitors and regulatory T cells. Innovative approaches for therapeutic modulation of this immunosuppressive adoptive DC immunotherapy will be highlighted, which is necessary for future personalized therapeutic applications. Copyright: © 2024 The Author(s). Published by IMR Press.
Engineered Artesunate-Naphthalimide Hybrid Dual Drug for Synergistic Multimodal Therapy against Experimental Murine Lymphoma
(American Chemical Society, 2024) Debapriya RoyMahapatra; Ranjeet Singh; Ugir Hossain Sk; Partha Pratim Manna
Lymphoma can effectively be treated with a chemotherapy regimen that is associated with adverse side effects due to increasing drug resistance, so there is an emergent need for alternative small-molecule inhibitors to overcome the resistance that occurs in lymphoma management and overall increase the prognosis rate. A new series of substituted naphthalimide moieties conjugated via ester and amide linkages with artesunate were designed, synthesized, and characterized. In addition to the conjugates, to further achieve a theranostic molecule, FITC was incorporated via a multistep synthesis process. DNA binding studies of these selected derivatives by ultraviolet-visible (UV-vis), fluorescence spectroscopy, intercalating dye (EtBr, acridine orange)-DNA competitive assay, and minor groove binding dye Hoechst 33342-DNA competitive assay suggested that the synthesized novel molecules intercalated between the two strands of DNA due to its naphthalimide moiety and its counterpart artesunate binds with the minor groove of DNA. Napthalimide-artesunate conjugates inhibit the growth of lymphoma and induce apoptosis, including ready incorporation and reduction in cell viability. The remodeled drug has a significant tumoricidal effect against solid DL tumors developed in BALB/c mice in a dose-dependent manner. The novel drug appears to inhibit metastasis and increase the survival of the treated animals compared with untreated littermates. © 2024 American Chemical Society.
Enhanced bioactivity, biocompatibility and mechanical behavior of strontium substituted bioactive glasses
(Elsevier Ltd, 2016) Sampath Kumar Arepalli; Himanshu Tripathi; Sumit Kumar Hira; Partha Pratim Manna; Ram Pyare; S.P.Singh
Strontium contained biomaterials have been reported as a potential bioactive material for bone regeneration, as it reduces bone resorption and stimulates bone formation. In the present investigation, the bioactive glasses were designed to partially substitute SrO for SiO2 in Na2O–CaO–SrO–P2O5–SiO2 system. This work demonstrates that the substitution of SrO for SiO2 has got significant benefit than substitution for CaO in the bioactive glass. Bioactivity was assessed by the immersion of the samples in simulated body fluid for different intervals. The formation of hydroxy carbonate apatite layer was identified by X-ray diffractometry, scanning electron microscopy (SEM) and energy dispersive spectroscopy. The elastic modulus of the bioactive glasses was measured and found to increase with increasing SrO for SiO2. The blood compatibility of the samples was evaluated. In vitro cell culture studies of the samples were performed using human osteosarcoma U2-OS cell lines and found a significant improvement in cell viability and proliferation. The investigation showed enhancement in bioactivity, mechanical and biological properties of the strontia substituted for silica in glasses. Thus, these bioactive glasses would be highly potential for bone regeneration. © 2016
Enhanced in vivo biocompatibility of magnesia-contained bioactive glasses
(Springer International Publishing, 2019) Sampath Kumar Arepalli; Himanshu Tripathi; Partha Pratim Manna; Paliwal Pankaj; Sairam Krishnamurthy; Shashikant C. U. Patne; Ram Pyare; S.P. Singh
Human blood compatibility of previously prepared magnesia-doped bioactive glass samples was evaluated by hemolysis assay. The in vivo evaluation was carried out using a rat model in which a hole was made in the rat femur bone by drilling and the bioactive glass samples were implanted in the cavity. Histological examination had demonstrated the better bone regeneration and blood vessel formation as compared to the reference one. The in vivo complete blood count (CBC) was also analyzed at different time periods. The in vivo results of magnesium-containing bioactive glasses had shown improved bioactivity as well as better biocompatibility. © 2018, Australian Ceramic Society.