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 -