Photothermal treatment of liver cancer with albumin-conjugated gold nanoparticles initiates Golgi Apparatus-ER dysfunction and caspase-3 apoptotic pathway activation by selective targeting of Gp60 receptor

Int J Nanomedicine. 2015 Aug 26:10:5435-45. doi: 10.2147/IJN.S86495. eCollection 2015.

Abstract

We present a method of enhanced laser thermal ablation of HepG2 cells based on a simple gold nanoparticle (GNP) carrier system such as serum albumin (Alb), and demonstrate its selective therapeutic efficacy compared with normal hepatocyte cells. HepG2 or hepatocytes were treated with Alb-GNPs at various concentrations and various incubation times, and further irradiated using a 2 W, 808 nm laser. Darkfield microscopy and immunochemical staining was used to demonstrate the selective internalization of Alb-GNPs inside the HepG2 cells via Gp60 receptors targeting. The postirradiation apoptotic rate of HepG2 cells treated with Alb-GNPs ranged from 25.8% (for 5 μg/mL) to 48.2% (for 50 μg/mL) at 60 seconds, while at 30 minutes the necrotic rate increased from 35.7% (5 μg/mL) to 52.3% (50 μg/mL), P-value <0.001. Significantly lower necrotic rates were obtained when human hepatocytes were treated with Alb-GNPs in a similar manner. We also showed by means of immunocytochemistry that photothermal treatment of Alb-conjugated GNPs in liver cancer initiates Golgi apparatus-endoplasmic reticulum dysfunction with consequent caspase-3 apoptotic pathway activation and cellular apoptosis. The presented results may become a new method of treating cancer cells by selective therapeutic vectors using nanolocalized thermal ablation by laser heating.

Keywords: HepG2 cells; albumin; functionalization; gold nanoparticles; laser irradiation; liver cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Carcinoma, Hepatocellular / pathology
  • Caspase 3 / metabolism*
  • Drug Carriers / chemistry*
  • Endoplasmic Reticulum / metabolism
  • Gold / chemistry*
  • Golgi Apparatus / metabolism
  • Hep G2 Cells / drug effects
  • Humans
  • Hyperthermia, Induced
  • Immunohistochemistry
  • Lasers
  • Liver Neoplasms / pathology*
  • Metal Nanoparticles / chemistry*
  • Necrosis
  • Photochemistry
  • Serum Albumin / metabolism*
  • Sialoglycoproteins / metabolism*

Substances

  • Drug Carriers
  • Serum Albumin
  • Sialoglycoproteins
  • sialoglycoprotein gp60
  • Gold
  • CASP3 protein, human
  • Caspase 3