A novel theranostic gold nanorods- and Adriamycin-loaded micelle for EpCAM targeting, laser ablation, and photoacoustic imaging of cancer stem cells in hepatocellular carcinoma

Int J Nanomedicine. 2019 Mar 13:14:1877-1892. doi: 10.2147/IJN.S197265. eCollection 2019.

Abstract

Introduction and purpose: Cancer stem cells (CSCs) present a higher capacity to evade being killed by cancer agents and developing chemoresistance, thus leading to failure of conventional anticancer therapeutics. Nanomaterials specifically designed for targeting and treating not only tumor cells, but also CSCs, may encompass therapeutic and diagnostic tools, thus successfully eradicating the tumor.

Materials and methods: Polymeric micelles simultaneously loaded with gold nanorods (GNRs) and Adriamycin were prepared and used as a novel therapeutic and diagnostic weapon. Epithelial cell adhesion molecule (EpCAM) is an important CSC surface marker and has been exploited in this work as an active targeting agent. Photoacoustic imaging was applied for GNR individuation and tissue recognition.

Results: The nanosystem was demonstrated to be able to elicit effective targeting of cancer cells and cause their killing, in particular under laser ablation. Moreover, ex vivo photoacoustic imaging is able to clearly identify tumor regions thanks to GNR's contrast.

Conclusion: The nanosystem can be considered a powerful and promising theranostic weapon for hepatocellular carcinoma treatment.

Keywords: EpCAM; cancer stem cells; drug delivery; gold nanorods; photoacoustic imaging; photothermal therapy.

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Doxorubicin / administration & dosage*
  • Drug Delivery Systems / instrumentation
  • Drug Delivery Systems / methods*
  • Epithelial Cell Adhesion Molecule / immunology*
  • Gold / chemistry
  • Humans
  • Laser Therapy
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / pathology
  • Male
  • Mice, Inbred C57BL
  • Micelles
  • Molecular Targeted Therapy / instrumentation
  • Molecular Targeted Therapy / methods
  • Nanotubes / chemistry*
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / pathology
  • Photoacoustic Techniques / instrumentation
  • Photoacoustic Techniques / methods*
  • Theranostic Nanomedicine / instrumentation
  • Theranostic Nanomedicine / methods
  • Xenograft Model Antitumor Assays

Substances

  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • Micelles
  • Gold
  • Doxorubicin