Fucoidan-Doxorubicin Nanoparticles Targeting P-Selectin for Effective Breast Cancer Therapy

Carbohydr Polym. 2020 Dec 1:249:116837. doi: 10.1016/j.carbpol.2020.116837. Epub 2020 Jul 31.

Abstract

Fucoidan, a type of sulfated polysaccharide known for its anticoagulant, anti-tumor and anti-inflammatory effects, has been reported to have strong affinity towards P-selectin. P-selectin, which plays an important role in metastasis by enhancing the adhesion of cancer cells to endothelium and activated platelets in distant organs, is overexpressed on many cancer types. This study demonstrates the synthesis of a fucoidan-based drug delivery system for minimizing the side effects of doxorubicin (Dox) with the help of active targeting toward P-selectin. Fucoidan-doxorubicin nanoparticles (FU-Dox NPs), developed by direct conjugation of Dox to the fucoidan backbone, showed a well-controlled size distribution and sustained release. The active targeting capability of FU-Dox NPs toward P-selectin resulted in enhanced cellular uptake and cytotoxicity against the MDA-MB-231 cell line with high P-selectin expression compared to the MDA-MB-468 cell line with low P-selectin expression.

Keywords: Active targeting; Doxorubicin; Drug delivery; Fucoidan; P-selectin.

MeSH terms

  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Delivery Systems*
  • Female
  • Humans
  • Molecular Targeted Therapy
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • P-Selectin / antagonists & inhibitors*
  • Polysaccharides / chemistry*

Substances

  • Antibiotics, Antineoplastic
  • P-Selectin
  • Polysaccharides
  • SELP protein, human
  • Doxorubicin
  • fucoidan