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 | |
| Publication status | Published - 1 Oct 2018 |
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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
}
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
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.
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
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 -