Nanoparticle core stability and surface functionalization drive the mTOR signaling pathway in hepatocellular cell...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cell Biology

Background:

• Functionalized nanoparticles are promising for biomedical applications.
• Nanoparticle surface chemistry and biodegradability critically influence their cellular effects.
• Understanding nanoparticle-cell interactions is key for developing safe nano-therapeutics.

Purpose of the Study:

• To investigate the impact of surface functionalization and biodegradability on nanoparticle-induced cellular responses.
• To elucidate the molecular mechanisms underlying the differential effects of polystyrene and silica nanoparticles on liver cancer cells.
• To explore the potential of nanoparticles in controlling cell proliferation and viability via mTOR signaling.

Main Methods:

• Treatment of hepatocellular carcinoma Huh7 and HepG2 cells with amino-functionalized polystyrene nanoparticles (PS-NH2) and amino- or hydroxyl-functionalized silica nanoparticles (Si-NH2).
• Assessment of cell viability, cell death pathways, lysosomal and mitochondrial membrane integrity.
• Analysis of mTOR signaling pathway activation.
• Comparison of effects between biodegradable and non-biodegradable nanoparticles with identical characteristics.

Main Results:

• PS-NH2 nanoparticles triggered cell death in Huh7 cells, while Si-NH2 nanoparticles did not.
• PS-NH2 nanoparticles induced lysosomal destabilization and mitochondrial damage, preceding cell death.
• Si-NH2 nanoparticles activated mTOR signaling and enhanced proliferation in both Huh7 and HepG2 cells.
• Biodegradable silica nanoparticles exhibited opposite cellular effects compared to non-biodegradable polystyrene nanoparticles.

Conclusions:

• Nanoparticle biodegradability and surface functionalization are critical determinants of cellular fate.
• PS-NH2 nanoparticles induce cell death through lysosomal and mitochondrial disruption.
• Si-NH2 nanoparticles promote cell proliferation via mTOR pathway activation.
• Functionalized nanoparticles can be engineered to control hepatocellular carcinoma cell behavior, offering potential for novel nano-therapeutics.