Negative-charge-functionalized mesoporous silica nanoparticles as drug vehicles targeting hepatocellular carcinoma

Int J Pharm. 2014 Oct 20;474(1-2):223-31. doi: 10.1016/j.ijpharm.2014.08.027. Epub 2014 Aug 19.

Abstract

In this paper, a series of doxorubicin-loaded and negative-charge-functionalized mesoporous silica nanoparticles (DOX-MSN/COOH) was successfully prepared and used for imaging and targeting therapy of hepatocellular carcinoma. The nanoparticles were uniform and negatively charged, with a diameter of about 55 nm, and a zeta potential of -20 mV. In vitro study showed that the nanoparticles could easily be endocytosed by liver cancer cells (HepG2) and were well-accumulated in the liver by passive targeting. In vivo study proved the ability of DOX-MSN/COOH to inhibit the tumor growth and prolong the survival time of mice bearing hepatocellular carcinoma in situ, giving better results than free DOX. More importantly, histological examination showed no histopathological abnormalities of normal liver cells and heart cells after the administration of DOX-MSN/COOH, while the treatment with free DOX caused damage to those cells. In conclusion, DOX-MSN/COOH exhibited enhanced antitumor efficacy as well as reduced side effects for liver cancer therapy.

Keywords: Antitumor; Biodistribution; Doxorubicin; Liver tumor in situ; Mesoporous silica nanoparticles; Survival rate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry
  • Doxorubicin / metabolism
  • Doxorubicin / pharmacokinetics
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemistry*
  • Drug Screening Assays, Antitumor
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Mice
  • Mice, Inbred ICR
  • Mice, Nude
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry*
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Particle Size
  • Porosity
  • Silicon Dioxide / administration & dosage
  • Silicon Dioxide / chemistry*
  • Structure-Activity Relationship
  • Surface Properties
  • Tissue Distribution

Substances

  • Drug Carriers
  • Silicon Dioxide
  • Doxorubicin