Synthesis of theranostic epithelial cell adhesion molecule targeted mesoporous silica nanoparticle with gold gatekeeper for hepatocellular carcinoma

Nanomedicine (Lond). 2017 Jun;12(11):1261-1279. doi: 10.2217/nnm-2017-0028. Epub 2017 May 18.

Abstract

Aim: In this study, we report the fabrication of epithelial cell adhesion molecule targeted 5-fluorouracil (5-FU) encapsulated PEGylated mesoporous silica nanoparticles (NPs) hybridized with gold NPs (PEG-Au@Si-5-FU) as gatekeeper for theranostic applications.

Materials & methods: The prepared targeted and nontargeted formulations were evaluated in vitro in terms of their cellular internalization and toxicity. The prepared theranostic hybrid system was also implemented for computed tomography of HepG2 tumor-bearing nude mice in vivo.

Results: Fluorescence microscopy and MTT assay demonstrated that the developed epithelial cell adhesion molecule-PEG-Au@Si-5-FU had higher cytotoxicity than nontargeted PEG-Au@Si-5-FU in 2D and 3D HepG2 cell cultures. Moreover, the targeted hybrid system was preferentially accumulated in HepG2 tumor cells in vitro and in vivo.

Conclusion: This work introduces a novel strategy for developing multimodal NPs via nanoparticulate hybrid materials.

Keywords: 5-fluorouracil; EpCAM; aptamer; gatekeeper; gold nanoparticles; silica.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Cell Survival / drug effects
  • Drug Carriers / chemistry
  • Drug Delivery Systems
  • Epithelial Cell Adhesion Molecule / metabolism*
  • Fluorouracil / administration & dosage*
  • Fluorouracil / therapeutic use
  • Gold / chemistry*
  • Hep G2 Cells
  • Humans
  • Liver / drug effects
  • Liver / metabolism
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Mice, Inbred C57BL
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Silicon Dioxide / chemistry*
  • Theranostic Nanomedicine

Substances

  • Antimetabolites, Antineoplastic
  • Drug Carriers
  • Epithelial Cell Adhesion Molecule
  • Gold
  • Silicon Dioxide
  • Fluorouracil