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 (journal)peer-review

17 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 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

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

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this