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

Research output: Contribution to journalArticle

1 Citation (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 languageEnglish
Pages (from-to)645-658
Number of pages14
JournalMaterials Science and Engineering C
Volume91
Early online date4 May 2018
DOIs
Publication statusPublished - 1 Oct 2018

Fingerprint

Polyunsaturated fatty acids
Clathrin
fatty acids
Cytotoxicity
Unsaturated Fatty Acids
breast
Tumors
drugs
tumors
cancer
docetaxel
Cell death
Assays
Cells
Pharmaceutical Preparations
Rhodamine 123
Flow cytometry
Fluorescence microscopy
hematology
Toxicity

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

Cite this

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.
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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.",
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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",
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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 journalArticle

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 - 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.

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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

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KW - Clathrin/metabolism

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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

U2 - 10.1016/j.msec.2018.05.010

DO - 10.1016/j.msec.2018.05.010

M3 - Article

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JO - Materials Science and Engineering C

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