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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.

Mocan L, Matea C, Tabaran FA, Mosteanu O, Pop T, Mocan T, Iancu C - Int J Nanomedicine (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Nanomedicine Department, Regional Institute of Gastroenterology and Hepatology "Octavian Fodor", University of Medicine and Pharmacy, "Iuliu Hatieganu", Croitorilor, Cluj-Napoca, Romania ; Department of Surgery, University of Medicine and Pharmacy, "Iuliu Hatieganu", Croitorilor, Cluj-Napoca, Romania.

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.

No MeSH data available.


Related in: MedlinePlus

GNPs albumin-mediated in vitro endocytosis mechanism in human liver cancer cells.Notes: Exposure to 50 μg/mL Alb-GNPs for 1 hour, 37°C. Dark field light microscopy images of Alb-GNPs uptake into Hep G2 cells or Hep B5 cells (control). Magnification: 80×.Abbreviations: AU, absorbance units; Alb-GNPs, albumin-conjugated gold nanoparticles.
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f2-ijn-10-5435: GNPs albumin-mediated in vitro endocytosis mechanism in human liver cancer cells.Notes: Exposure to 50 μg/mL Alb-GNPs for 1 hour, 37°C. Dark field light microscopy images of Alb-GNPs uptake into Hep G2 cells or Hep B5 cells (control). Magnification: 80×.Abbreviations: AU, absorbance units; Alb-GNPs, albumin-conjugated gold nanoparticles.

Mentions: In order to shed light on the molecular mechanisms involved in the specific uptake of Alb-GNPs in HepG2 cells, we investigated the possibility that a 60 kDa glycoprotein, Gp60, which is known to function in Alb transcytosis in malignant cells, was involved in the selective uptake of Alb bound to GNPs. To accomplish this, we allowed the 50 μg/mL Alb-GNP treated cells (1 hour) to incorporate Cy3–anti-Gp60 Ab for 30 minutes at 37°C. To that end, we obtained fluorescent images demonstrating the activation of the Gp60 receptors as suggested by Cy3 fluorescence (Figure 2B).


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.

Mocan L, Matea C, Tabaran FA, Mosteanu O, Pop T, Mocan T, Iancu C - Int J Nanomedicine (2015)

GNPs albumin-mediated in vitro endocytosis mechanism in human liver cancer cells.Notes: Exposure to 50 μg/mL Alb-GNPs for 1 hour, 37°C. Dark field light microscopy images of Alb-GNPs uptake into Hep G2 cells or Hep B5 cells (control). Magnification: 80×.Abbreviations: AU, absorbance units; Alb-GNPs, albumin-conjugated gold nanoparticles.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554431&req=5

f2-ijn-10-5435: GNPs albumin-mediated in vitro endocytosis mechanism in human liver cancer cells.Notes: Exposure to 50 μg/mL Alb-GNPs for 1 hour, 37°C. Dark field light microscopy images of Alb-GNPs uptake into Hep G2 cells or Hep B5 cells (control). Magnification: 80×.Abbreviations: AU, absorbance units; Alb-GNPs, albumin-conjugated gold nanoparticles.
Mentions: In order to shed light on the molecular mechanisms involved in the specific uptake of Alb-GNPs in HepG2 cells, we investigated the possibility that a 60 kDa glycoprotein, Gp60, which is known to function in Alb transcytosis in malignant cells, was involved in the selective uptake of Alb bound to GNPs. To accomplish this, we allowed the 50 μg/mL Alb-GNP treated cells (1 hour) to incorporate Cy3–anti-Gp60 Ab for 30 minutes at 37°C. To that end, we obtained fluorescent images demonstrating the activation of the Gp60 receptors as suggested by Cy3 fluorescence (Figure 2B).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Nanomedicine Department, Regional Institute of Gastroenterology and Hepatology "Octavian Fodor", University of Medicine and Pharmacy, "Iuliu Hatieganu", Croitorilor, Cluj-Napoca, Romania ; Department of Surgery, University of Medicine and Pharmacy, "Iuliu Hatieganu", Croitorilor, Cluj-Napoca, Romania.

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.

No MeSH data available.


Related in: MedlinePlus