Undaria pinnatifida fucoidan nanoparticles loaded with quinacrine attenuate growth and metastasis of pancreatic cancer

Int J Biol Macromol. 2021 Feb 15:170:284-297. doi: 10.1016/j.ijbiomac.2020.12.109. Epub 2020 Dec 17.

Abstract

Pancreatic cancer is a devastating gastrointestinal tumor with limited Chemotherapeutic options. Treatment is restricted by its poor vascularity and dense surrounding stroma. Quinacrine is a repositioned drug with an anticancer activity but suffers a limited ability to reach tumor cells. This could be enhanced using nanotechnology by the preparation of quinacrine-loaded Undaria pinnatifida fucoidan nanoparticles. The system exploited fucoidan as both a delivery system of natural origin and active targeting ligand. Lactoferrin was added as a second active targeting ligand. Single and dual-targeted particles prepared through nanoprecipitation and ionic interaction respectively were appraised. Both particles showed a size lower than 200 nm, entrapment efficiency of 80% and a pH-dependent release of the drug in the acidic environment of the tumor. The anticancer activity of quinacrine was enhanced by 5.7 folds in dual targeted particles compared to drug solution with a higher ability to inhibit migration and invasion of cancer. In vivo, these particles showed a 68% reduction in tumor volume compared to only 20% for drug solution. In addition, they showed a higher animals' survival rate with no hepatotoxicity. Hence, these particles could be an effective option for the eradication of pancreatic cancer cells.

Keywords: Fucoidan; Lactoferrin; P-selectin; Pancreatic cancer; Quinacrine; Undaria pinnatifida.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry
  • Neoplasm Metastasis / drug therapy
  • Pancreatic Neoplasms / drug therapy*
  • Polysaccharides / metabolism
  • Polysaccharides / pharmacology*
  • Quinacrine / metabolism
  • Quinacrine / pharmacology
  • Undaria / metabolism*

Substances

  • Polysaccharides
  • fucoidan
  • Quinacrine