Decorating protein nanospheres with lactoferrin enhances oral COX-2 inhibitor/herbal therapy of hepatocellular carcinoma

Nanomedicine (Lond). 2018 Oct;13(19):2377-2395. doi: 10.2217/nnm-2018-0134. Epub 2018 Oct 22.

Abstract

Aim: Lactoferrin (LF)-targeted gliadin nanoparticles (GL-NPs) were developed for targeted oral therapy of hepatocellular carcinoma.

Materials & methods: Celecoxib and diosmin were incorporated in the hydrophobic matrix of GL-NPs whose surface was decorated with LF by electrostatic interaction for binding to asialoglycoprotein receptors overexpressed by liver cancer cells.

Results: Targeted GL-NPs showed enhanced cytotoxic activity and increased cellular uptake in liver tumor cells compared with nontargeted NPs. Moreover, they demonstrated superior in vivo antitumor effects including reduction in the expression levels of tumor biomarkers and induction of caspase-mediated apoptosis. Ex vivo imaging of isolated organs exhibited extensive accumulation of NPs in livers more than other organs.

Conclusion: LF-targeted GL-NPs could be considered as an efficient nanoplatform for targeted oral drug delivery for liver cancer therapy.

Keywords: COX-2 inhibitors; diosmin; gliadin nanoparticles; hepatocellular carcinoma; lactoferrin-targeting; oral delivery.

MeSH terms

  • Administration, Oral
  • Animals
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 Inhibitors / administration & dosage
  • Doxorubicin / administration & dosage
  • Doxorubicin / chemistry
  • Drug Delivery Systems
  • Hep G2 Cells
  • Humans
  • Lactoferrin / chemistry
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Mice
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Nanospheres / administration & dosage
  • Nanospheres / adverse effects
  • Phytotherapy*
  • Tissue Distribution
  • Xenograft Model Antitumor Assays

Substances

  • Cyclooxygenase 2 Inhibitors
  • Doxorubicin
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Lactoferrin