Gold nanoparticles affect the antioxidant status in selected normal human cells

Area of Science:

• Nanomedicine
• Toxicology
• Cell Biology

Background:

• Gold nanoparticles (AuNPs) are explored for biomedical applications.
• Polyallylamine (PAA) coating and Cetuximab (Ctxb) conjugation modify AuNP properties.
• Understanding AuNP cytotoxicity in different cell types is crucial for in vivo safety.

Purpose of the Study:

• Evaluate cytotoxicity of AuNPs-PAA and AuNPs-PAA-Ctxb.
• Compare effects on normal (HK-2, THLE-2, TIME) and cancer (A431, MDA-MB-453) cells.
• Investigate mechanisms of AuNP-induced cell death.

Main Methods:

• Cytotoxicity assays on various cell lines.
• Assessment of nanoparticle-cell interactions.
• Measurement of thioredoxin reductase (TrxR) and glutathione reductase (GR) activity.
• Mitochondrial membrane potential evaluation.
• Apoptosis detection.
• Co-incubation with N-acetyl L-cysteine (NAC) to assess oxidative stress.

Main Results:

• Cetuximab conjugation increased AuNP-cell interaction but decreased cytotoxicity.
• TIME cells showed highest sensitivity, followed by THLE-2, MDA-MB-453, HK-2, and A431.
• Sensitivity correlated with TrxR/GR inhibition and mitochondrial depolarization.
• Apoptosis was induced in a concentration- and time-dependent manner.
• NAC treatment reduced apoptosis and mitochondrial depolarization, confirming oxidative stress involvement.

Conclusions:

• AuNP-PAA-Ctxb exhibits differential cytotoxicity across cell types.
• Inhibition of TrxR/GR and mitochondrial dysfunction are key mechanisms.
• Oxidative stress plays a significant role in AuNP-induced apoptosis.
• Findings aid in identifying sensitive tissues and understanding in vivo risks of AuNPs.