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Article ; Online: Nanoparticles in cancer chemotherapy.

Banerjee, Deboshri / Sengupta, Shiladitya

Progress in molecular biology and translational science

2011 Volume 104, Page(s) 489–507

Abstract: Nanotechnology has evolved as an exciting platform in the field of anticancer research with promises to improve the pharmacology of current cancer therapeutics. Nanoparticles confer several advantages over that of free drugs, including their capability ... ...

Abstract	Nanotechnology has evolved as an exciting platform in the field of anticancer research with promises to improve the pharmacology of current cancer therapeutics. Nanoparticles confer several advantages over that of free drugs, including their capability to carry high payloads of drugs, with prolonged half-life and reduced toxicity of the drugs, and increased targeting efficiency. The wide variety of nanovectors, coupled with the different methods available to conjugate or encapsulate therapeutic and/or imaging agents within, provide us with opportunities to fine-tune the pharmacological properties of these agents and open up new vistas in anticancer research. Here, we will discuss the physicochemical properties of different nanoparticles, their impact on tumor targeting, and their current status in the clinics with respect to cancer chemotherapy.
MeSH term(s)	Clinical Trials as Topic ; Diagnostic Imaging ; Drug Delivery Systems ; Humans ; Nanoparticles/chemistry ; Nanotechnology ; Neoplasms/drug therapy
Language	English
Publishing date	2011
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2471995-X
ISSN	1878-0814 ; 0079-6603 ; 1877-1173
ISSN (online)	1878-0814
ISSN	0079-6603 ; 1877-1173
DOI	10.1016/B978-0-12-416020-0.00012-7
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Article ; Online: Nanotechnology-mediated targeting of tumor angiogenesis

Banerjee Deboshri / Harfouche Rania / Sengupta Shiladitya

Vascular Cell, Vol 3, Iss 1, p

2011 Volume 3

Abstract: Abstract Angiogenesis is disregulated in many diseased states, most notably in cancer. An emerging strategy for the development of therapies targeting tumor-associated angiogenesis is to harness the potential of nanotechnology to improve the pharmacology ...

Abstract	Abstract Angiogenesis is disregulated in many diseased states, most notably in cancer. An emerging strategy for the development of therapies targeting tumor-associated angiogenesis is to harness the potential of nanotechnology to improve the pharmacology of chemotherapeutics, including anti-angiogenic agents. Nanoparticles confer several advantages over that of free drugs, including their capability to carry high payloads of therapeutic agents, confer increased half-life and reduced toxicity to the drugs, and provide means for selective targeting of the tumor tissue and vasculature. The plethora of nanovectors available, in addition to the various methods available to combine them with anti-angiogenic drugs, allows researchers to fine-tune the pharmacological profile of the drugs ad infinitum . Use of nanovectors has also opened up novel avenues for non-invasive imaging of tumor angiogenesis. Herein, we review the types of nanovector and therapeutic/diagnostic agent combinations used in targeting tumor angiogenesis.
Keywords	Diseases of the circulatory (Cardiovascular) system ; RC666-701 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Cardiovascular ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Nanotechnology-mediated targeting of tumor angiogenesis.

Banerjee, Deboshri / Harfouche, Rania / Sengupta, Shiladitya

Vascular cell

2011 Volume 3, Issue 1, Page(s) 3

Abstract: Angiogenesis is disregulated in many diseased states, most notably in cancer. An emerging strategy for the development of therapies targeting tumor-associated angiogenesis is to harness the potential of nanotechnology to improve the pharmacology of ... ...

Abstract	Angiogenesis is disregulated in many diseased states, most notably in cancer. An emerging strategy for the development of therapies targeting tumor-associated angiogenesis is to harness the potential of nanotechnology to improve the pharmacology of chemotherapeutics, including anti-angiogenic agents. Nanoparticles confer several advantages over that of free drugs, including their capability to carry high payloads of therapeutic agents, confer increased half-life and reduced toxicity to the drugs, and provide means for selective targeting of the tumor tissue and vasculature. The plethora of nanovectors available, in addition to the various methods available to combine them with anti-angiogenic drugs, allows researchers to fine-tune the pharmacological profile of the drugs ad infinitum. Use of nanovectors has also opened up novel avenues for non-invasive imaging of tumor angiogenesis. Herein, we review the types of nanovector and therapeutic/diagnostic agent combinations used in targeting tumor angiogenesis.
Language	English
Publishing date	2011-01-31
Publishing country	England
Document type	Journal Article
ZDB-ID	2595417-9
ISSN	2045-824X ; 2045-824X
ISSN (online)	2045-824X
ISSN	2045-824X
DOI	10.1186/2045-824X-3-3
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Article ; Online: Mechanistic studies of Gemcitabine-loaded nanoplatforms in resistant pancreatic cancer cells

Papa Anne-Laure / Basu Sudipta / Sengupta Poulomi / Banerjee Deboshri / Sengupta Shiladitya / Harfouche Rania

BMC Cancer, Vol 12, Iss 1, p

2012 Volume 419

Abstract: Abstract Background Pancreatic cancer remains the deadliest of all cancers, with a mortality rate of 91%. Gemcitabine is considered the gold chemotherapeutic standard, but only marginally improves life-span due to its chemical instability and low cell ... ...

Abstract	Abstract Background Pancreatic cancer remains the deadliest of all cancers, with a mortality rate of 91%. Gemcitabine is considered the gold chemotherapeutic standard, but only marginally improves life-span due to its chemical instability and low cell penetrance. A new paradigm to improve Gemcitabine’s therapeutic index is to administer it in nanoparticles, which favour its delivery to cells when under 500 nm in diameter. Although promising, this approach still suffers from major limitations, as the choice of nanovector used as well as its effects on Gemcitabine intracellular trafficking inside pancreatic cancer cells remain unknown. A proper elucidation of these mechanisms would allow for the elaboration of better strategies to engineer more potent Gemcitabine nanotherapeutics against pancreatic cancer. Methods Gemcitabine was encapsulated in two types of commonly used nanovectors, namely poly(lactic-co-glycolic acid) (PLGA) and cholesterol-based liposomes, and their physico-chemical parameters assessed in vitro . Their mechanisms of action in human pancreatic cells were compared with those of the free drug, and with each others, using cytotoxity, apoptosis and ultrastructural analyses. Results Physico-chemical analyses of both drugs showed high loading efficiencies and sizes of less than 200 nm, as assessed by dynamic light scattering (DLS) and transmission electron microscopy (TEM), with a drug release profile of at least one week. These profiles translated to significant cytotoxicity and apoptosis, as well as distinct intracellular trafficking mechanisms, which were most pronounced in the case of PLGem showing significant mitochondrial, cytosolic and endoplasmic reticulum stresses. Conclusions Our study demonstrates how the choice of nanovector affects the mechanisms of drug action and is a crucial determinant of Gemcitabine intracellular trafficking and potency in pancreatic cancer settings.
Keywords	Gemcitabine ; Pancreatic cancer ; Liposome ; Poly(lactic-co-glycolic acid) ; Transmission electron microscopy ; Neoplasms. Tumors. Oncology. Including cancer and carcinogens ; RC254-282 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Oncology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610
Language	English
Publishing date	2012-09-01T00:00:00Z
Publisher	BioMed Central
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mechanistic studies of Gemcitabine-loaded nanoplatforms in resistant pancreatic cancer cells.

Papa, Anne-Laure / Basu, Sudipta / Sengupta, Poulomi / Banerjee, Deboshri / Sengupta, Shiladitya / Harfouche, Rania

BMC cancer

2012 Volume 12, Page(s) 419

Abstract: Background: Pancreatic cancer remains the deadliest of all cancers, with a mortality rate of 91%. Gemcitabine is considered the gold chemotherapeutic standard, but only marginally improves life-span due to its chemical instability and low cell ... ...

Abstract	Background: Pancreatic cancer remains the deadliest of all cancers, with a mortality rate of 91%. Gemcitabine is considered the gold chemotherapeutic standard, but only marginally improves life-span due to its chemical instability and low cell penetrance. A new paradigm to improve Gemcitabine's therapeutic index is to administer it in nanoparticles, which favour its delivery to cells when under 500 nm in diameter. Although promising, this approach still suffers from major limitations, as the choice of nanovector used as well as its effects on Gemcitabine intracellular trafficking inside pancreatic cancer cells remain unknown. A proper elucidation of these mechanisms would allow for the elaboration of better strategies to engineer more potent Gemcitabine nanotherapeutics against pancreatic cancer. Methods: Gemcitabine was encapsulated in two types of commonly used nanovectors, namely poly(lactic-co-glycolic acid) (PLGA) and cholesterol-based liposomes, and their physico-chemical parameters assessed in vitro. Their mechanisms of action in human pancreatic cells were compared with those of the free drug, and with each others, using cytotoxity, apoptosis and ultrastructural analyses. Results: Physico-chemical analyses of both drugs showed high loading efficiencies and sizes of less than 200 nm, as assessed by dynamic light scattering (DLS) and transmission electron microscopy (TEM), with a drug release profile of at least one week. These profiles translated to significant cytotoxicity and apoptosis, as well as distinct intracellular trafficking mechanisms, which were most pronounced in the case of PLGem showing significant mitochondrial, cytosolic and endoplasmic reticulum stresses. Conclusions: Our study demonstrates how the choice of nanovector affects the mechanisms of drug action and is a crucial determinant of Gemcitabine intracellular trafficking and potency in pancreatic cancer settings.
MeSH term(s)	Antimetabolites, Antineoplastic/administration & dosage ; Antimetabolites, Antineoplastic/chemistry ; Cell Line, Tumor ; Cholesterol/chemistry ; Deoxycytidine/administration & dosage ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/chemistry ; Humans ; Lactic Acid/chemistry ; Liposomes/chemical synthesis ; Liposomes/chemistry ; Microscopy, Electron, Transmission ; Nanotechnology/methods ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/ultrastructure ; Polyglycolic Acid/chemistry ; Polylactic Acid-Polyglycolic Acid Copolymer
Chemical Substances	Antimetabolites, Antineoplastic ; Liposomes ; Deoxycytidine (0W860991D6) ; Polylactic Acid-Polyglycolic Acid Copolymer (1SIA8062RS) ; Polyglycolic Acid (26009-03-0) ; Lactic Acid (33X04XA5AT) ; Cholesterol (97C5T2UQ7J) ; gemcitabine (B76N6SBZ8R)
Language	English
Publishing date	2012-09-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1471-2407
ISSN (online)	1471-2407
DOI	10.1186/1471-2407-12-419
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Article ; Online: The impact of surfactants on Fe(III)-TAML-catalyzed oxidations by peroxides: accelerations, decelerations, and loss of activity.

Banerjee, Deboshri / Apollo, Frank M / Ryabov, Alexander D / Collins, Terrence J

Chemistry (Weinheim an der Bergstrasse, Germany)

2009 Volume 15, Issue 39, Page(s) 10199–10209

Abstract: Iron(III) complexes of tetraamidato macrocyclic ligands (TAMLs), [Fe{4-XC(6)H(3)-1,2-(NCOCMe(2)NCO)(2)CR(2)}(OH(2))](-), 1 (1 a: X = H, R = Me; 1 b: X = COOH, R = Me); 1 c: X = CONH(CH(2))(2)COOH, R = Me; 1 d: CONH(CH(2))(2)NMe(2), R = Me; 1 e: X = CONH( ... ...

Abstract	Iron(III) complexes of tetraamidato macrocyclic ligands (TAMLs), [Fe{4-XC(6)H(3)-1,2-(NCOCMe(2)NCO)(2)CR(2)}(OH(2))](-), 1 (1 a: X = H, R = Me; 1 b: X = COOH, R = Me); 1 c: X = CONH(CH(2))(2)COOH, R = Me; 1 d: CONH(CH(2))(2)NMe(2), R = Me; 1 e: X = CONH(CH(2))(2)NMe(3) (+), R = Me; 1 f: X = H, R = F), have been tested as catalysts for the oxidative decolorization of Orange II and Sudan III dyes by hydrogen peroxide and tert-butyl hydroperoxide in the presence of micelles that are neutral (Triton X-100), positively charged (cetyltrimethylammonium bromide, CTAB), and negatively charged (sodium dodecyl sulfate, SDS). The previously reported mechanism of catalysis involves the formation of an oxidized intermediate from 1 and ROOH (k(I)) followed by dye bleaching (k(II)). The micellar effects on k(I) and k(II) have been separately studied and analyzed by using the Berezin pseudophase model of micellar catalysis. The largest micellar acceleration in terms of k(I) occurs for the 1 a-tBuOOH-CTAB system. At pH 9.0-10.5 the rate constant k(I) increased by approximately five times with increasing CTAB concentration and then gradually decreased. There was no acceleration at higher pH, presumably owing to the deprotonation of the axial water ligand of 1 a in this pH range. The k(I) value was only slightly affected by SDS (in the oxidation of Orange II), but was strongly decelerated by Triton X-100. No oxidation of the water-insoluble, hydrophobic dye Sudan III was observed in the presence of the SDS micelles. The k(II) value was accelerated by cationic CTAB micelles when the hydrophobic primary oxidant tert-butyl hydroperoxide was used. It is hypothesized that tBuOOH may affect the CTAB micelles and increase the binding of the oxidized catalysts. The tBuOOH-CTAB combination accelerated both of the catalysis steps k(I) and k(II).
Language	English
Publishing date	2009-10-05
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1478547-x
ISSN	1521-3765 ; 0947-6539
ISSN (online)	1521-3765
ISSN	0947-6539
DOI	10.1002/chem.200900729
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Article: Multivalent Display and Receptor-Mediated Endocytosis of Transferrin on Virus-Like Particles

Banerjee, Deboshri / Liu, Allen P / Voss, Neil R / Schmid, Sandra L / Finn, M.G

Chembiochem. 2010 June 14, v. 11, no. 9

2010

Abstract: The structurally regular and stable self-assembled capsids derived from viruses can be used as scaffolds for the display of multiple copies of cell- and tissue-targeting molecules and therapeutic agents in a convenient and well-defined manner. The human ... ...

Abstract	The structurally regular and stable self-assembled capsids derived from viruses can be used as scaffolds for the display of multiple copies of cell- and tissue-targeting molecules and therapeutic agents in a convenient and well-defined manner. The human iron-transfer protein transferrin, a high affinity ligand for receptors upregulated in a variety of cancers, has been arrayed on the exterior surface of the protein capsid of bacteriophage Qβ. Selective oxidation of the sialic acid residues on the glycan chains of transferrin was followed by introduction of a terminal alkyne functionality through an oxime linkage. Attachment of the protein to azide-functionalized Qβ capsid particles in an orientation allowing access to the receptor binding site was accomplished by the CuI-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction. Transferrin conjugation to Qβ particles allowed specific recognition by transferrin receptors and cellular internalization through clathrin-mediated endocytosis, as determined by fluorescence microscopy on cells expressing GFP-labeled clathrin light chains. By testing Qβ particles bearing different numbers of transferrin molecules, it was demonstrated that cellular uptake was proportional to ligand density, but that internalization was inhibited by equivalent concentrations of free transferrin. These results suggest that cell targeting with transferrin can be improved by local concentration (avidity) effects.
Language	English
Dates of publication	2010-0614
Size	p. 1273-1279.
Publishing place	Wiley-VCH Verlag
Document type	Article
ZDB-ID	2020469-3
ISSN	1439-7633 ; 1439-4227
ISSN (online)	1439-7633
ISSN	1439-4227
DOI	10.1002/cbic.201000125
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Article ; Online: Multivalent display and receptor-mediated endocytosis of transferrin on virus-like particles.

Banerjee, Deboshri / Liu, Allen P / Voss, Neil R / Schmid, Sandra L / Finn, M G

Chembiochem : a European journal of chemical biology

2010 Volume 11, Issue 9, Page(s) 1273–1279

Abstract	The structurally regular and stable self-assembled capsids derived from viruses can be used as scaffolds for the display of multiple copies of cell- and tissue-targeting molecules and therapeutic agents in a convenient and well-defined manner. The human iron-transfer protein transferrin, a high affinity ligand for receptors upregulated in a variety of cancers, has been arrayed on the exterior surface of the protein capsid of bacteriophage Qbeta. Selective oxidation of the sialic acid residues on the glycan chains of transferrin was followed by introduction of a terminal alkyne functionality through an oxime linkage. Attachment of the protein to azide-functionalized Qbeta capsid particles in an orientation allowing access to the receptor binding site was accomplished by the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction. Transferrin conjugation to Qbeta particles allowed specific recognition by transferrin receptors and cellular internalization through clathrin-mediated endocytosis, as determined by fluorescence microscopy on cells expressing GFP-labeled clathrin light chains. By testing Qbeta particles bearing different numbers of transferrin molecules, it was demonstrated that cellular uptake was proportional to ligand density, but that internalization was inhibited by equivalent concentrations of free transferrin. These results suggest that cell targeting with transferrin can be improved by local concentration (avidity) effects.
MeSH term(s)	Alkynes/chemistry ; Allolevivirus/chemistry ; Allolevivirus/metabolism ; Animals ; Capsid Proteins/chemistry ; Capsid Proteins/metabolism ; Catalysis ; Cell Line ; Clathrin/metabolism ; Copper ; Endocytosis ; Flow Cytometry ; Haplorhini ; Humans ; Ligands ; Transferrin/chemistry ; Transferrin/metabolism
Chemical Substances	Alkynes ; Capsid Proteins ; Clathrin ; Ligands ; Transferrin ; Copper (789U1901C5)
Language	English
Publishing date	2010-03-28
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2020469-3
ISSN	1439-7633 ; 1439-4227
ISSN (online)	1439-7633
ISSN	1439-4227
DOI	10.1002/cbic.201000125
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Article: Total degradation of fenitrothion and other organophosphorus pesticides by catalytic oxidation employing Fe-TAML peroxide activators.

Chanda, Arani / Khetan, Sushil K / Banerjee, Deboshri / Ghosh, Anindya / Collins, Terrence J

Journal of the American Chemical Society

2006 Volume 128, Issue 37, Page(s) 12058–12059

Abstract: A Fe-TAML/H2O2 catalytic oxidation process achieves facile in-solution total degradation of fenitrothion and two other organophosphorus (OP) pesticides. Degradation products have been identified and quantified providing evidence for oxidative hydrolysis, ...

Abstract	A Fe-TAML/H2O2 catalytic oxidation process achieves facile in-solution total degradation of fenitrothion and two other organophosphorus (OP) pesticides. Degradation products have been identified and quantified providing evidence for oxidative hydrolysis, oxidative desulfuration, perhydrolysis, and deep oxidation. Degradation pathways can be selected by pH control to completely obviate all toxic residuals. Aquatic toxicity assays support the environmental compatibility of the degradation process.
Language	English
Publishing date	2006-09-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	3155-0
ISSN	1520-5126 ; 0002-7863
ISSN (online)	1520-5126
ISSN	0002-7863
DOI	10.1021/ja064017e
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Article: Both GABAB receptor activation and blockade exacerbated anhedonic aspects of nicotine withdrawal in rats

Vlachou, Styliani / Paterson, Neil E / Guery, Sebastien / Kaupmann, Klemens / Froestl, Wolfgang / Banerjee, Deboshri / Finn, M.G / Markou, Athina

European journal of pharmacology. 2011 Mar. 25, v. 655, no. 1-3

2011

Abstract: Nicotine dependence is maintained by the aversive, depression-like effects of nicotine withdrawal and the rewarding effects of acute nicotine. GABAB receptor antagonists exhibit antidepressant-like effects in rodents, whereas GABAB receptor agonists ... ...

Abstract	Nicotine dependence is maintained by the aversive, depression-like effects of nicotine withdrawal and the rewarding effects of acute nicotine. GABAB receptor antagonists exhibit antidepressant-like effects in rodents, whereas GABAB receptor agonists attenuate the rewarding effects of nicotine. Recent studies with GABAB receptor positive modulators showed that these compounds represent potentially improved medications for the treatment of nicotine dependence because of fewer side-effects than GABAB receptor agonists. Thus, GABAB receptor agonists and antagonists, and GABAB receptor positive modulators may have efficacy as smoking cessation aids by targeting different aspects of nicotine dependence and withdrawal. The present study assessed the effects of the GABAB receptor agonist CGP44532, the GABAB receptor antagonist CGP56433A, and the GABAB receptor positive modulator BHF177 on the anhedonic aspects of nicotine withdrawal. Rats were prepared with stimulating electrodes in the posterior lateral hypothalamus. After establishing stable intracranial self-stimulation (ICSS) thresholds, rats were prepared with subcutaneous osmotic minipumps delivering either nicotine or saline for 7 or 14days. ICSS thresholds were assessed 6h post-pump removal. Thirty hours after pump removal, CGP44532, CGP56433A, and BHF177 were administered 30min prior to ICSS testing. Both GABAB receptor activation (CGP44532 and BHF177) and blockade (CGP56433A) elevated ICSS thresholds in all groups, resulting in exacerbated effects of nicotine withdrawal in the nicotine-treated groups. These similar effects of GABAB receptor activation and blockade on the anhedonic depression-like aspects of nicotine withdrawal were surprising and perhaps reflect differential efficacy of these compounds at presynaptic hetero- and autoreceptors, as well as postsynaptic, GABAB receptors.
Keywords	acute effects ; adverse effects ; agonists ; antagonists ; electrodes ; hypothalamus ; nicotine ; pharmacology ; rats ; receptors
Language	English
Dates of publication	2011-0325
Size	p. 52-58.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	80121-5
ISSN	1879-0712 ; 0014-2999
ISSN (online)	1879-0712
ISSN	0014-2999
DOI	10.1016/j.ejphar.2011.01.009
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