Vascular targeted chitosan-derived nanoparticles as docetaxel carriers for gastric cancer therapy

Int J Biol Macromol. 2019 Apr 1;126:662-672. doi: 10.1016/j.ijbiomac.2018.12.262. Epub 2018 Dec 29.

Abstract

A gastric cancer angiogenesis marker peptide, GX1, is promising to be a desirable ligand for anti-angiogenesis targeted drug of gastric cancer treatment. In this study, GX1 was utilized to fabricate a multifunctional vascular targeting docetaxel (DCT)-loaded nanoparticle with N-deoxycholic acid glycol chitosan (DGC) as the carrier and GX1-PEG-deoxycholic acid (GPD) conjugate as the targeting ligand. The mean size of obtained GX1-DGC-DCT was 150.9 nm with a narrow size distribution and their shape was spherical with smooth surface texture. The in vitro drug release test revealed a sustained release manner and an acid pH could accelerate the release compared with the neutral pH. Furthermore, GX1-DGC-DCT showed stronger cytotoxicity against co-cultured gastric cancer cells and human umbilical vein endothelial cells (co-HUVEC) than DCT within 100 μM. In addition, GX1 efficiently enhanced the cellular uptake of nanoparticles in co-HUVEC cells as confirmed by confocal fluorescence scanning microscopy. Moreover, in vivo delivery of GX1-DGC-DCT was demonstrated to inhibit tumor growth in SGC791 tumor-bearing mice with tumor inhibition rate (TIR) of 67.05% and no weight loss of mice was observed. The anti-tumor effects were further confirmed by H&E and TUNEL analysis. Therefore, this new drug delivery system represents a potential strategy for gastric cancer therapy.

Keywords: Chitosan; Docetaxel; Targeted drug delivery.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Blood Vessels / drug effects*
  • Cell Death / drug effects
  • Chitosan / chemical synthesis
  • Chitosan / chemistry
  • Deoxycholic Acid / chemical synthesis
  • Deoxycholic Acid / chemistry
  • Docetaxel / pharmacology
  • Docetaxel / therapeutic use*
  • Drug Carriers / chemistry*
  • Drug Delivery Systems*
  • Drug Liberation
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry
  • Spectroscopy, Fourier Transform Infrared
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • glycol-chitosan
  • Deoxycholic Acid
  • Docetaxel
  • Polyethylene Glycols
  • Chitosan