In Vitro Evaluation of NLS-DTX Activity in Triple-Negative Breast Cancer

Molecules. 2022 Aug 2;27(15):4920. doi: 10.3390/molecules27154920.

Abstract

Cancer is one of the most lethal diseases in the world, and the development and improvement of treatments used in cancer therapies are extremely important for a better quality of life for patients. In view of the current problems in drug administration such as low solubility and adverse effects, the activity of a solid lipid nanoparticle containing docetaxel (SLN-DTX), a drug already used in conventional therapies, was evaluated in a cell line (MDA-MB-231) of one of the most aggressive types of breast cancer with the worst prognosis, triple-negative breast cancer. Viability tests indicated that SLN-DTX has a greater dependence on the treatment dose when compared to the free drug, which indicates a more controlled release of the drug, and both reduced viability by around 50% at a concentration of 1 µg/mL after 72 h. Transmission electron microscopy (TEM) and confocal and light microscopy analyses indicated that after treatment the cells enter a mitotic catastrophe, characteristic of antimitotic drugs that usually make cells progress to death or senescence. Cells treated with both DTX and SLN-DTX showed significant inhibition of mobility, 73.6% and 66.5% when treated with SLN-DTX and DTX, respectively, compared to the 11.4% of the control after 72 h, characteristics that are very relevant in tumor development and progression. SLN-DTX demonstrated its great potential as a nanocarrier by maintaining and improving the drug's action in the MDA-MB-231 cell line.

Keywords: docetaxel; solid lipid nanoparticle; triple-negative breast cancer.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Cell Line, Tumor
  • Drug Carriers / therapeutic use
  • Humans
  • Liposomes
  • Nanoparticles*
  • Quality of Life
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / pathology

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Lipid Nanoparticles
  • Liposomes

Grants and funding

This research was funded by the National Council for Scientific and Technological Development—CNPq (401957/2016-0, 302355/2016-2); Coordination for the Improvement of Higher Level Personnel—CAPES (0001); Funding Body for Studies and Projects—FINEP (01.08.0457.00); Federal District Research Support Foundation—FAPDF (00193.00000920/2020-23).