pH sensitive doxorubicin-loaded nanoparticle based on Radix pseudostellariae protein-polysaccharide conjugate and its improvement on HepG2 cellular uptake of doxorubicin

Food Chem Toxicol. 2020 Feb:136:111099. doi: 10.1016/j.fct.2019.111099. Epub 2019 Dec 26.

Abstract

Nanoparticles based on Radix pseudostellariae protein-polysaccharide conjugates were self-assembled via pH adjustment and thermal treatment. The fabricated nanoparticles (CP3) were spherical with narrow size distribution of 125.0 nm in diameter. The doxorubicin (DOX) -loaded CP3 nanoparticles exhibited pH-sensitive release behavior and accelerated the release of DOX under the acidic pH simulating tumor microenvironment and endosomal pH. In HepG2 uptake studies, CP3-DOX nanoparticles notably improved the internalization of DOX, which was 1.56-fold compared with free DOX. CP3-DOX nanoparticles could serve as P-glycoprotein efflux pump inhibitor and be internalized into HepG2 cells via clathrin-dependent endocytosis. Moreover, the cytotoxicity effect of DOX on HepG2 cells was elevated after the encapsulation by CP3, with a lower IC50 value of 0.25 μg/mL. The findings suggested that the pH-sensitive CP3-DOX nanoparticles has a great potential in facilitating the efficacy of DOX in cancer cells, and the obtained CP3 could be a good candidate as nanocarrier for the encapsulation and delivery of functional compounds.

Keywords: Cellular uptake; Doxorubicin; Nanoparticle; Protein-polysaccharide conjugate; Radix pseudostellariae; pH-sensitive release.

MeSH terms

  • Biological Transport
  • Caryophyllaceae / chemistry*
  • Doxorubicin / chemistry*
  • Doxorubicin / metabolism*
  • Drug Carriers / chemistry*
  • Drug Delivery Systems
  • Endocytosis
  • Hep G2 Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Nanoparticles / chemistry*
  • Plant Extracts / chemistry*
  • Polysaccharides / chemistry*

Substances

  • Drug Carriers
  • Plant Extracts
  • Polysaccharides
  • Doxorubicin