Rajkumar Banerjee - Academia.edu (original) (raw)
Papers by Rajkumar Banerjee
Molecules
Delivering nucleic acids into the endothelium has great potential in treating vascular diseases. ... more Delivering nucleic acids into the endothelium has great potential in treating vascular diseases. However, endothelial cells, which line the vasculature, are considered as sensitive in nature and hard to transfect. Low transfection efficacies in endothelial cells limit their potential therapeutic applications. Towards improving the transfection efficiency, we made an effort to understand the internalization of lipoplexes into the cells, which is the first and most critical step in nucleic acid transfections. In this study, we demonstrated that the transient modulation of caveolae/lipid rafts mediated endocytosis with the cholesterol-sequestrating agents, nystatin, filipin III, and siRNA against Cav-1, which significantly increased the transfection properties of cationic lipid-(2-hydroxy-N-methyl-N,N-bis(2-tetradecanamidoethyl)ethanaminium chloride), namely, amide liposomes in combination with 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) (AD Liposomes) in liver sinusoidal endo...
ACS Applied Materials & Interfaces, 2022
Real-time monitored controlled delivery of carbon monoxide (CO) has recently emerged as a promisi... more Real-time monitored controlled delivery of carbon monoxide (CO) has recently emerged as a promising strategy for effective cancer therapy. However, it remains a challenge to develop CO releasing molecules (CORMs) that enable a dose dependent spatiotemporal release of CO in the "phototherapeutic window" with real time monitoring ability.
La presente invention concerne une formulation dans laquelle des glycolipides et des phospholipid... more La presente invention concerne une formulation dans laquelle des glycolipides et des phospholipides, isoles d'echantillons de gomme de son de riz, ont ete utilises conjointement avec des lipides transporteurs de genes pour tester leur efficacite dans l'administration selective de genes dans les cellules cancereuses. Cette formulation n'a pas induit une administration efficace des genes dans les cellules non cancereuses, ce qui montre qu'il est possible d'utiliser cette formulation pour administrer des produits therapeutiques anticancereux dans les cellules cancereuses sans produire de toxicite liee au traitement dans les cellules normales.
Journal of Drug Delivery Science and Technology, 2020
Cancer treatment necessitates targeted and efficient drug delivery to reduce drug-mediated advers... more Cancer treatment necessitates targeted and efficient drug delivery to reduce drug-mediated adverse collateral effects. We develop herein a new liposomal delivery system which targets both CD13 receptor-positive cancer epithelial and angiogenic endothelial cells using the homing peptide (NGR), as liposome surface bound targeting ligand. The ligand NGR, upon covalent conjugation to a C16-aliphatic twin-chain lipid via a lysine (K) spacer, afforded C16-lipopeptide. Importantly, the circulation stable liposomes of NGRKC16-lipopeptide containing encapsulated withaferin-A (WFA), a multipotent drug, exhibited receptor-mediated uptake and apoptosismediated cell death in both CD13 receptor-positive pancreatic cancer cells and angiogenic endothelial cells, while the other non-targeting control formulation failed to do so. In a Chick embryo angiogenesis assay, the targeted formulation selectively inhibited angiogenesis, i.e., sprouting of new blood vessels from the pre-existing blood vessels. These finding revealed therapeutic potential of WFA-encapsulated liposomal formulation of NGRKC16-lipopeptide for simultaneous killing of CD13-positive pancreatic cancer as well as angiogenic endothelial cells. As angiogenesis, endorsed by endothelial cells and aggressiveness in tumor epithelial cells are symbiotically related, the presently described CD13 receptor selective WFA-encapsulated liposomal formulation of NGRKC16-lipopeptide may find future use for the treatment of aggressive pancreatic cancer.
Journal of Materials Chemistry B, 2020
BBB-crossing amphetamine decorated cationic lipid nanoparticle co-loaded with paclitaxel and PDL-... more BBB-crossing amphetamine decorated cationic lipid nanoparticle co-loaded with paclitaxel and PDL-1 siRNA enhances survivability of orthotopic glioblastoma bearing mice.
Autophagy, 2012
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since t... more In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field
Nanoscale Advances, 2019
A carbon nanosphere-based dual strategy to target tumor-associated macrophages and tumor cells in... more A carbon nanosphere-based dual strategy to target tumor-associated macrophages and tumor cells in glioma lesions within the brain.
Molecular Pharmaceutics, 2020
Glioblastoma multiforme (GBM) is one of the most aggressive tumors with median survival of only 1... more Glioblastoma multiforme (GBM) is one of the most aggressive tumors with median survival of only 15 months. Effective therapeutics need to overcome the formidable challenge of crossing the blood brain barrier (BBB). Receptors and transporters overexpressed on BCECs are being used for designing liposomes, polymers, polymeric micelles, peptides and dendrimer-based drug carriers for combating brain tumors. Herein, using orthotopic mouse glioblastoma model, we show that co-delivering small molecule inhibitor of JAK/STAT pathway (WP1066) and STAT3siRNA with nanometric (100-150 nm) α5β1 integrin receptor selective liposomes of RGDK-lipopeptide hold therapeutic promise in combating glioblastoma. The selective accumulation of intravenously administered near infrared (NIR)-dye labeled α5β1 integrin receptor selective liposomes of RGDK-lipopeptide in the mouse brain tumor tissue. Importantly, we show that i.v. injection of WP1066 (a commercially sold small molecule inhibitor of JAK/STAT pathway) & STAT3siRNA co-solubilized within the liposomes of RGDK-lipopeptide leads to significant inhibition (>350% compared to the untreated mice group) of orthotopically growing mouse glioblastoma. The present strategy may find future use in combating GBM.
The objective of drug delivery systems is to deliver a drug effectively, specifically to the site... more The objective of drug delivery systems is to deliver a drug effectively, specifically to the site of action, in a controlled manner and to achieve greater efficacy and minimize the toxic effects compared to conventional drugs. Liposomes are the leading drug delivery systems for the systemic (intravenous) administration of drugs. The real breakthrough developments in the area during the past 15 years have resulted in the approval of several liposomal drugs, and the appearance of many unique biomedical products and technologies involving liposomes. There are now liposomal formulations of conventional drugs that have received clinical approval and many others in clinical trials that bring benefits of reduced toxicity and enhanced efficacy for the treatment of cancer and other life-threatening diseases.
Handbook of Oxidative Stress in Cancer: Mechanistic Aspects
Organic & Biomolecular Chemistry
Endosomal escape is one of the barriers for the efficient liposomal gene delivery.
Bioorganic Chemistry
Natural antioxidants and vitamins have potential to protect biological systems from peroxidative ... more Natural antioxidants and vitamins have potential to protect biological systems from peroxidative damage induced by peroxyl radicals, α-tocopherol (Vitamin E, lipid soluble) and ascorbic acid (vitamin C, water soluble), well known natural antioxidant molecules. In the present study we described the synthesis and biological evaluation of hybrid of these two natural antioxidants with each other via ammonium di-ethylether linker, Toc-As in gene delivery. Two control cationic lipids N14-As and Toc-NOH are designed in such a way that one is with ascorbic acid moiety and no tocopherol moiety; another is with tocopherol moiety and no ascorbic acid moiety respectively. All the three cationic lipids can form self-assembled aggregates. The antioxidant efficiencies of the three lipids were compared with free ascorbic acid. The cationic lipids (Toc-As, N14-As and Toc-NOH) were formulated individually with a well-known fusogenic co-lipid DOPE and characterization studies such as DNA binding, heparin displacement, size, charge, circular dichroism were performed. The biological characterization studies such as cell viability assay and in vitro transfection studies were carried out with the above formulations in HepG2, Neuro-2a, CHO andHEK-293T cell lines. The three formulations showed their transfection efficiencies with highest in Toc-As, moderate inN14-As and least in Toc-NOH. Interestingly, the transfection efficiency observed with the antioxidant based conjugated lipid Toc-As is found to be approximately two and half fold higher than the commercially available lipofectamine 2000 at 4:1 charge ratio in Hep G2 cell lines. In the other cell lines studied the efficiency of Toc-As is found to be either higher or similarly active compared to lipofectamine 2000. The physicochemical characterization results show that Toc-As lipid is showing maximum antioxidant potency, strong binding with pDNA, least size and optimal zeta potential. It is also found to be least toxic in all the cell lines studied especially in Neuro-2a cell lines when compared to other two lipids. In summary, the designed antioxidant lipid can be exploited as a delivering system for treating ROS related diseases such as malignancy, brain stroke, etc.
Prayogik Rasayan
Glucocorticoid receptor (GR) is expressed in the cytoplasm of almost all cells, if not all of can... more Glucocorticoid receptor (GR) is expressed in the cytoplasm of almost all cells, if not all of cancer and non-cancer cells. Moreover, unlike many other factors implicated with cancer, it is neither overexpressed nor is it expressed on cell-membrane surface to qualify logically as a viable target for treating cancer. GR is importantly linked with alternate pathway of energy metabolism in cancer cells and our research indicated that cancer cells possibly tend to avoid activation of GR which would have otherwise instigate that energy demanding alternate pathway called gluconeogenesis. We discovered a way to induce cancer cell-selective GR-transactivation which leads to among many things, gluconeogenesis, reversal of epithelial-to-mesenchymal transition (EMT), drug- sensitization in drug-resistant cancer cells etc. Thus, we proved, although it warrants further studies, that GR in cancer cells behave differently and hence it can be a viable target for the treatment of cancer.
WIREs Nanomedicine and Nanobiotechnology
Journal of Cellular Biochemistry
Molecules
Delivering nucleic acids into the endothelium has great potential in treating vascular diseases. ... more Delivering nucleic acids into the endothelium has great potential in treating vascular diseases. However, endothelial cells, which line the vasculature, are considered as sensitive in nature and hard to transfect. Low transfection efficacies in endothelial cells limit their potential therapeutic applications. Towards improving the transfection efficiency, we made an effort to understand the internalization of lipoplexes into the cells, which is the first and most critical step in nucleic acid transfections. In this study, we demonstrated that the transient modulation of caveolae/lipid rafts mediated endocytosis with the cholesterol-sequestrating agents, nystatin, filipin III, and siRNA against Cav-1, which significantly increased the transfection properties of cationic lipid-(2-hydroxy-N-methyl-N,N-bis(2-tetradecanamidoethyl)ethanaminium chloride), namely, amide liposomes in combination with 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) (AD Liposomes) in liver sinusoidal endo...
ACS Applied Materials & Interfaces, 2022
Real-time monitored controlled delivery of carbon monoxide (CO) has recently emerged as a promisi... more Real-time monitored controlled delivery of carbon monoxide (CO) has recently emerged as a promising strategy for effective cancer therapy. However, it remains a challenge to develop CO releasing molecules (CORMs) that enable a dose dependent spatiotemporal release of CO in the "phototherapeutic window" with real time monitoring ability.
La presente invention concerne une formulation dans laquelle des glycolipides et des phospholipid... more La presente invention concerne une formulation dans laquelle des glycolipides et des phospholipides, isoles d'echantillons de gomme de son de riz, ont ete utilises conjointement avec des lipides transporteurs de genes pour tester leur efficacite dans l'administration selective de genes dans les cellules cancereuses. Cette formulation n'a pas induit une administration efficace des genes dans les cellules non cancereuses, ce qui montre qu'il est possible d'utiliser cette formulation pour administrer des produits therapeutiques anticancereux dans les cellules cancereuses sans produire de toxicite liee au traitement dans les cellules normales.
Journal of Drug Delivery Science and Technology, 2020
Cancer treatment necessitates targeted and efficient drug delivery to reduce drug-mediated advers... more Cancer treatment necessitates targeted and efficient drug delivery to reduce drug-mediated adverse collateral effects. We develop herein a new liposomal delivery system which targets both CD13 receptor-positive cancer epithelial and angiogenic endothelial cells using the homing peptide (NGR), as liposome surface bound targeting ligand. The ligand NGR, upon covalent conjugation to a C16-aliphatic twin-chain lipid via a lysine (K) spacer, afforded C16-lipopeptide. Importantly, the circulation stable liposomes of NGRKC16-lipopeptide containing encapsulated withaferin-A (WFA), a multipotent drug, exhibited receptor-mediated uptake and apoptosismediated cell death in both CD13 receptor-positive pancreatic cancer cells and angiogenic endothelial cells, while the other non-targeting control formulation failed to do so. In a Chick embryo angiogenesis assay, the targeted formulation selectively inhibited angiogenesis, i.e., sprouting of new blood vessels from the pre-existing blood vessels. These finding revealed therapeutic potential of WFA-encapsulated liposomal formulation of NGRKC16-lipopeptide for simultaneous killing of CD13-positive pancreatic cancer as well as angiogenic endothelial cells. As angiogenesis, endorsed by endothelial cells and aggressiveness in tumor epithelial cells are symbiotically related, the presently described CD13 receptor selective WFA-encapsulated liposomal formulation of NGRKC16-lipopeptide may find future use for the treatment of aggressive pancreatic cancer.
Journal of Materials Chemistry B, 2020
BBB-crossing amphetamine decorated cationic lipid nanoparticle co-loaded with paclitaxel and PDL-... more BBB-crossing amphetamine decorated cationic lipid nanoparticle co-loaded with paclitaxel and PDL-1 siRNA enhances survivability of orthotopic glioblastoma bearing mice.
Autophagy, 2012
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since t... more In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field
Nanoscale Advances, 2019
A carbon nanosphere-based dual strategy to target tumor-associated macrophages and tumor cells in... more A carbon nanosphere-based dual strategy to target tumor-associated macrophages and tumor cells in glioma lesions within the brain.
Molecular Pharmaceutics, 2020
Glioblastoma multiforme (GBM) is one of the most aggressive tumors with median survival of only 1... more Glioblastoma multiforme (GBM) is one of the most aggressive tumors with median survival of only 15 months. Effective therapeutics need to overcome the formidable challenge of crossing the blood brain barrier (BBB). Receptors and transporters overexpressed on BCECs are being used for designing liposomes, polymers, polymeric micelles, peptides and dendrimer-based drug carriers for combating brain tumors. Herein, using orthotopic mouse glioblastoma model, we show that co-delivering small molecule inhibitor of JAK/STAT pathway (WP1066) and STAT3siRNA with nanometric (100-150 nm) α5β1 integrin receptor selective liposomes of RGDK-lipopeptide hold therapeutic promise in combating glioblastoma. The selective accumulation of intravenously administered near infrared (NIR)-dye labeled α5β1 integrin receptor selective liposomes of RGDK-lipopeptide in the mouse brain tumor tissue. Importantly, we show that i.v. injection of WP1066 (a commercially sold small molecule inhibitor of JAK/STAT pathway) & STAT3siRNA co-solubilized within the liposomes of RGDK-lipopeptide leads to significant inhibition (>350% compared to the untreated mice group) of orthotopically growing mouse glioblastoma. The present strategy may find future use in combating GBM.
The objective of drug delivery systems is to deliver a drug effectively, specifically to the site... more The objective of drug delivery systems is to deliver a drug effectively, specifically to the site of action, in a controlled manner and to achieve greater efficacy and minimize the toxic effects compared to conventional drugs. Liposomes are the leading drug delivery systems for the systemic (intravenous) administration of drugs. The real breakthrough developments in the area during the past 15 years have resulted in the approval of several liposomal drugs, and the appearance of many unique biomedical products and technologies involving liposomes. There are now liposomal formulations of conventional drugs that have received clinical approval and many others in clinical trials that bring benefits of reduced toxicity and enhanced efficacy for the treatment of cancer and other life-threatening diseases.
Handbook of Oxidative Stress in Cancer: Mechanistic Aspects
Organic & Biomolecular Chemistry
Endosomal escape is one of the barriers for the efficient liposomal gene delivery.
Bioorganic Chemistry
Natural antioxidants and vitamins have potential to protect biological systems from peroxidative ... more Natural antioxidants and vitamins have potential to protect biological systems from peroxidative damage induced by peroxyl radicals, α-tocopherol (Vitamin E, lipid soluble) and ascorbic acid (vitamin C, water soluble), well known natural antioxidant molecules. In the present study we described the synthesis and biological evaluation of hybrid of these two natural antioxidants with each other via ammonium di-ethylether linker, Toc-As in gene delivery. Two control cationic lipids N14-As and Toc-NOH are designed in such a way that one is with ascorbic acid moiety and no tocopherol moiety; another is with tocopherol moiety and no ascorbic acid moiety respectively. All the three cationic lipids can form self-assembled aggregates. The antioxidant efficiencies of the three lipids were compared with free ascorbic acid. The cationic lipids (Toc-As, N14-As and Toc-NOH) were formulated individually with a well-known fusogenic co-lipid DOPE and characterization studies such as DNA binding, heparin displacement, size, charge, circular dichroism were performed. The biological characterization studies such as cell viability assay and in vitro transfection studies were carried out with the above formulations in HepG2, Neuro-2a, CHO andHEK-293T cell lines. The three formulations showed their transfection efficiencies with highest in Toc-As, moderate inN14-As and least in Toc-NOH. Interestingly, the transfection efficiency observed with the antioxidant based conjugated lipid Toc-As is found to be approximately two and half fold higher than the commercially available lipofectamine 2000 at 4:1 charge ratio in Hep G2 cell lines. In the other cell lines studied the efficiency of Toc-As is found to be either higher or similarly active compared to lipofectamine 2000. The physicochemical characterization results show that Toc-As lipid is showing maximum antioxidant potency, strong binding with pDNA, least size and optimal zeta potential. It is also found to be least toxic in all the cell lines studied especially in Neuro-2a cell lines when compared to other two lipids. In summary, the designed antioxidant lipid can be exploited as a delivering system for treating ROS related diseases such as malignancy, brain stroke, etc.
Prayogik Rasayan
Glucocorticoid receptor (GR) is expressed in the cytoplasm of almost all cells, if not all of can... more Glucocorticoid receptor (GR) is expressed in the cytoplasm of almost all cells, if not all of cancer and non-cancer cells. Moreover, unlike many other factors implicated with cancer, it is neither overexpressed nor is it expressed on cell-membrane surface to qualify logically as a viable target for treating cancer. GR is importantly linked with alternate pathway of energy metabolism in cancer cells and our research indicated that cancer cells possibly tend to avoid activation of GR which would have otherwise instigate that energy demanding alternate pathway called gluconeogenesis. We discovered a way to induce cancer cell-selective GR-transactivation which leads to among many things, gluconeogenesis, reversal of epithelial-to-mesenchymal transition (EMT), drug- sensitization in drug-resistant cancer cells etc. Thus, we proved, although it warrants further studies, that GR in cancer cells behave differently and hence it can be a viable target for the treatment of cancer.
WIREs Nanomedicine and Nanobiotechnology
Journal of Cellular Biochemistry