Clathrin-mediated endocytic uptake of PUFA enriched self-nanoemulsifying lipidic systems (SNELS) of an anticancer drug against triple negative cancer and DMBA induced preclinical tumor model

Rajneet Kaur Khurana; Rajendra Kumar; Balan Louis Gaspar; Gail Welsby; Philip Welsby; Prashant Kesharwani; O P Katare; Kamalinder K Singh; Bhupinder Singh

doi:10.1016/j.msec.2018.05.010

Clathrin-mediated endocytic uptake of PUFA enriched self-nanoemulsifying lipidic systems (SNELS) of an anticancer drug against triple negative cancer and DMBA induced preclinical tumor model

Rajneet Kaur Khurana, Rajendra Kumar, Balan Louis Gaspar, Gail Welsby, Philip Welsby, Prashant Kesharwani, O P Katare, Kamalinder K Singh, Bhupinder Singh

Undergraduate Medicine

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

The current studies envisage unravelling the underlying cellular internalisation mechanism of the systematically developed docetaxel (DTH) polyunsaturated fatty acid (PUFA) enriched self-nanoemulsifying lipidic micellar systems (SNELS). The concentration-, time- and cytotoxicity-related effects of DTH-SNELS on triple negative breast cancer (TNBC) MDA-MB-231 and non-TNBC MCF-7 cell lines were assessed through Presto-blue assay. Subsequently, rhodamine-123 (Rh-123) loaded SNELS were employed for evaluating their internalisation through flow cytometry and fluorescence microscopy, establishing it to be "clathrin-mediated" endocytic pathway. Apoptosis assay (65% cell death) and cell cycle distribution (47% inhibition at G2/M phase) further corroborated the cytotoxicity of DTH-SNELS towards cancerous cells. Biodistribution, histopathology and haematology studies indicated insignificant toxicity of the optimized formulation on vital organs. Preclinical anticancer efficacy studies using 7,12-dimethylbenzantracene (DMBA)-induced model construed significant reduction in breast tumor-volume. Overall, extensive in vitro and in vivo studies indicated the intracellular localization and cytotoxicity, suggesting DTH-SNELS as promising delivery systems for breast tumor therapeutics including TNBC.

Original language	English
Pages (from-to)	645-658
Number of pages	14
Journal	Materials Science and Engineering C
Volume	91
Early online date	4 May 2018
DOIs	https://doi.org/10.1016/j.msec.2018.05.010
Publication status	Published - 1 Oct 2018

Keywords

9,10-Dimethyl-1,2-benzanthracene
ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism
Animals
Antineoplastic Agents/pharmacology
Apoptosis/drug effects
Cell Cycle Checkpoints/drug effects
Cell Line, Tumor
Cell Proliferation/drug effects
Clathrin/metabolism
Docetaxel
Emulsions/chemistry
Endocytosis/drug effects
Fatty Acids, Unsaturated/metabolism
Female
Humans
Lipids/chemistry
Macrophages/drug effects
Mice
Nanoparticles/chemistry
Particle Size
RAW 264.7 Cells
Rats, Wistar
Static Electricity
Taxoids/pharmacology
Temperature
Time Factors
Triple Negative Breast Neoplasms/blood
Xenograft Model Antitumor Assays
Poly unsaturated fatty acid (PUFA)
Self-nanoemulsifying drug delivery systems
Clathrin mediated endocytosis
Breast cancer
Triple negative breast cancer (TNBC)
Apoptosis

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Dr PHILIP WELSBY
- Postgraduate Medical Education - Associate Head Medical Education - Postg
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Khurana, R. K., Kumar, R., Gaspar, B. L., Welsby, G., Welsby, P., Kesharwani, P., Katare, O. P., Singh, K. K., & Singh, B. (2018). Clathrin-mediated endocytic uptake of PUFA enriched self-nanoemulsifying lipidic systems (SNELS) of an anticancer drug against triple negative cancer and DMBA induced preclinical tumor model. Materials Science and Engineering C, 91, 645-658. https://doi.org/10.1016/j.msec.2018.05.010

Khurana, Rajneet Kaur ; Kumar, Rajendra ; Gaspar, Balan Louis ; Welsby, Gail ; Welsby, Philip ; Kesharwani, Prashant ; Katare, O P ; Singh, Kamalinder K ; Singh, Bhupinder. / Clathrin-mediated endocytic uptake of PUFA enriched self-nanoemulsifying lipidic systems (SNELS) of an anticancer drug against triple negative cancer and DMBA induced preclinical tumor model. In: Materials Science and Engineering C. 2018 ; Vol. 91. pp. 645-658.

@article{a1a10e9339c54064b50bad7052f10c01,

title = "Clathrin-mediated endocytic uptake of PUFA enriched self-nanoemulsifying lipidic systems (SNELS) of an anticancer drug against triple negative cancer and DMBA induced preclinical tumor model",

abstract = "The current studies envisage unravelling the underlying cellular internalisation mechanism of the systematically developed docetaxel (DTH) polyunsaturated fatty acid (PUFA) enriched self-nanoemulsifying lipidic micellar systems (SNELS). The concentration-, time- and cytotoxicity-related effects of DTH-SNELS on triple negative breast cancer (TNBC) MDA-MB-231 and non-TNBC MCF-7 cell lines were assessed through Presto-blue assay. Subsequently, rhodamine-123 (Rh-123) loaded SNELS were employed for evaluating their internalisation through flow cytometry and fluorescence microscopy, establishing it to be {"}clathrin-mediated{"} endocytic pathway. Apoptosis assay (65% cell death) and cell cycle distribution (47% inhibition at G2/M phase) further corroborated the cytotoxicity of DTH-SNELS towards cancerous cells. Biodistribution, histopathology and haematology studies indicated insignificant toxicity of the optimized formulation on vital organs. Preclinical anticancer efficacy studies using 7,12-dimethylbenzantracene (DMBA)-induced model construed significant reduction in breast tumor-volume. Overall, extensive in vitro and in vivo studies indicated the intracellular localization and cytotoxicity, suggesting DTH-SNELS as promising delivery systems for breast tumor therapeutics including TNBC.",

keywords = "9,10-Dimethyl-1,2-benzanthracene, ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism, Animals, Antineoplastic Agents/pharmacology, Apoptosis/drug effects, Cell Cycle Checkpoints/drug effects, Cell Line, Tumor, Cell Proliferation/drug effects, Clathrin/metabolism, Docetaxel, Emulsions/chemistry, Endocytosis/drug effects, Fatty Acids, Unsaturated/metabolism, Female, Humans, Lipids/chemistry, Macrophages/drug effects, Mice, Nanoparticles/chemistry, Particle Size, RAW 264.7 Cells, Rats, Wistar, Static Electricity, Taxoids/pharmacology, Temperature, Time Factors, Triple Negative Breast Neoplasms/blood, Xenograft Model Antitumor Assays, Poly unsaturated fatty acid (PUFA), Self-nanoemulsifying drug delivery systems, Clathrin mediated endocytosis, Breast cancer, Triple negative breast cancer (TNBC), Apoptosis",

author = "Khurana, {Rajneet Kaur} and Rajendra Kumar and Gaspar, {Balan Louis} and Gail Welsby and Philip Welsby and Prashant Kesharwani and Katare, {O P} and Singh, {Kamalinder K} and Bhupinder Singh",

note = "Funding Information: RK Khurana acknowledges the grants received from the University Grant Commission (UGC), New Delhi, India, to carry out the present research work, while working as a UGC Research Fellow under RFMS scheme, F. No. 5-(94)/2007/(BSR) . The use of biomedical facilities of University of Central Lancashire for the cell culture work is deeply acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Publisher Copyright: {\textcopyright} 2018 Elsevier B.V. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",

year = "2018",

month = oct,

day = "1",

doi = "10.1016/j.msec.2018.05.010",

language = "English",

volume = "91",

pages = "645--658",

journal = "Materials Science and Engineering C",

issn = "0928-4931",

publisher = "Elsevier BV",

}

Khurana, RK, Kumar, R, Gaspar, BL, Welsby, G , Welsby, P, Kesharwani, P, Katare, OP, Singh, KK & Singh, B 2018, 'Clathrin-mediated endocytic uptake of PUFA enriched self-nanoemulsifying lipidic systems (SNELS) of an anticancer drug against triple negative cancer and DMBA induced preclinical tumor model', Materials Science and Engineering C, vol. 91, pp. 645-658. https://doi.org/10.1016/j.msec.2018.05.010

Clathrin-mediated endocytic uptake of PUFA enriched self-nanoemulsifying lipidic systems (SNELS) of an anticancer drug against triple negative cancer and DMBA induced preclinical tumor model. / Khurana, Rajneet Kaur; Kumar, Rajendra; Gaspar, Balan Louis; Welsby, Gail ; Welsby, Philip; Kesharwani, Prashant; Katare, O P; Singh, Kamalinder K; Singh, Bhupinder.

In: Materials Science and Engineering C, Vol. 91, 01.10.2018, p. 645-658.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Clathrin-mediated endocytic uptake of PUFA enriched self-nanoemulsifying lipidic systems (SNELS) of an anticancer drug against triple negative cancer and DMBA induced preclinical tumor model

AU - Khurana, Rajneet Kaur

AU - Kumar, Rajendra

AU - Gaspar, Balan Louis

AU - Welsby, Gail

AU - Welsby, Philip

AU - Kesharwani, Prashant

AU - Katare, O P

AU - Singh, Kamalinder K

AU - Singh, Bhupinder

N1 - Funding Information: RK Khurana acknowledges the grants received from the University Grant Commission (UGC), New Delhi, India, to carry out the present research work, while working as a UGC Research Fellow under RFMS scheme, F. No. 5-(94)/2007/(BSR) . The use of biomedical facilities of University of Central Lancashire for the cell culture work is deeply acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Publisher Copyright: © 2018 Elsevier B.V. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.

PY - 2018/10/1

Y1 - 2018/10/1

N2 - The current studies envisage unravelling the underlying cellular internalisation mechanism of the systematically developed docetaxel (DTH) polyunsaturated fatty acid (PUFA) enriched self-nanoemulsifying lipidic micellar systems (SNELS). The concentration-, time- and cytotoxicity-related effects of DTH-SNELS on triple negative breast cancer (TNBC) MDA-MB-231 and non-TNBC MCF-7 cell lines were assessed through Presto-blue assay. Subsequently, rhodamine-123 (Rh-123) loaded SNELS were employed for evaluating their internalisation through flow cytometry and fluorescence microscopy, establishing it to be "clathrin-mediated" endocytic pathway. Apoptosis assay (65% cell death) and cell cycle distribution (47% inhibition at G2/M phase) further corroborated the cytotoxicity of DTH-SNELS towards cancerous cells. Biodistribution, histopathology and haematology studies indicated insignificant toxicity of the optimized formulation on vital organs. Preclinical anticancer efficacy studies using 7,12-dimethylbenzantracene (DMBA)-induced model construed significant reduction in breast tumor-volume. Overall, extensive in vitro and in vivo studies indicated the intracellular localization and cytotoxicity, suggesting DTH-SNELS as promising delivery systems for breast tumor therapeutics including TNBC.

AB - The current studies envisage unravelling the underlying cellular internalisation mechanism of the systematically developed docetaxel (DTH) polyunsaturated fatty acid (PUFA) enriched self-nanoemulsifying lipidic micellar systems (SNELS). The concentration-, time- and cytotoxicity-related effects of DTH-SNELS on triple negative breast cancer (TNBC) MDA-MB-231 and non-TNBC MCF-7 cell lines were assessed through Presto-blue assay. Subsequently, rhodamine-123 (Rh-123) loaded SNELS were employed for evaluating their internalisation through flow cytometry and fluorescence microscopy, establishing it to be "clathrin-mediated" endocytic pathway. Apoptosis assay (65% cell death) and cell cycle distribution (47% inhibition at G2/M phase) further corroborated the cytotoxicity of DTH-SNELS towards cancerous cells. Biodistribution, histopathology and haematology studies indicated insignificant toxicity of the optimized formulation on vital organs. Preclinical anticancer efficacy studies using 7,12-dimethylbenzantracene (DMBA)-induced model construed significant reduction in breast tumor-volume. Overall, extensive in vitro and in vivo studies indicated the intracellular localization and cytotoxicity, suggesting DTH-SNELS as promising delivery systems for breast tumor therapeutics including TNBC.

KW - 9,10-Dimethyl-1,2-benzanthracene

KW - ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism

KW - Animals

KW - Antineoplastic Agents/pharmacology

KW - Apoptosis/drug effects

KW - Cell Cycle Checkpoints/drug effects

KW - Cell Line, Tumor

KW - Cell Proliferation/drug effects

KW - Clathrin/metabolism

KW - Docetaxel

KW - Emulsions/chemistry

KW - Endocytosis/drug effects

KW - Fatty Acids, Unsaturated/metabolism

KW - Female

KW - Humans

KW - Lipids/chemistry

KW - Macrophages/drug effects

KW - Mice

KW - Nanoparticles/chemistry

KW - Particle Size

KW - RAW 264.7 Cells

KW - Rats, Wistar

KW - Static Electricity

KW - Taxoids/pharmacology

KW - Temperature

KW - Time Factors

KW - Triple Negative Breast Neoplasms/blood

KW - Xenograft Model Antitumor Assays

KW - Poly unsaturated fatty acid (PUFA)

KW - Self-nanoemulsifying drug delivery systems

KW - Clathrin mediated endocytosis

KW - Breast cancer

KW - Triple negative breast cancer (TNBC)

KW - Apoptosis

U2 - 10.1016/j.msec.2018.05.010

DO - 10.1016/j.msec.2018.05.010

M3 - Article

C2 - 30033299

VL - 91

SP - 645

EP - 658

JO - Materials Science and Engineering C

JF - Materials Science and Engineering C

SN - 0928-4931

ER -

Clathrin-mediated endocytic uptake of PUFA enriched self-nanoemulsifying lipidic systems (SNELS) of an anticancer drug against triple negative cancer and DMBA induced preclinical tumor model

Abstract

Keywords

Access to Document

Dr PHILIP WELSBY

Cite this