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

Specifically designed and functionalized nanoparticles hold great promise for biomedical applications. Yet, the applicability of nanoparticles is critically predetermined by their surface functionalization and biodegradability. Here we demonstrate that amino-functionalized polystyrene nanoparticles...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2017-11, Vol.7 (1), p.16049-16, Article 16049
Main Authors: Lunova, Mariia, Prokhorov, Andrey, Jirsa, Milan, Hof, Martin, Olżyńska, Agnieszka, Jurkiewicz, Piotr, Kubinová, Šárka, Lunov, Oleg, Dejneka, Alexandr
Format: Article
Language:English
Subjects:
Adsorption
Amines - chemistry
Animals
Apoptosis
Biodegradability
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Cattle
Cell death
Cell Line, Tumor
Cell lines
Cell Proliferation
Hepatocellular carcinoma
Liver cancer
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Lysosomes
Lysosomes - metabolism
Mitochondria
Nanoparticles
Nanoparticles - chemistry
Permeability
Polystyrene
Polystyrenes - chemistry
Protein Conformation
Ribonucleases - metabolism
Serum Albumin, Bovine - metabolism
Signal Transduction
Silica
Silicon Dioxide - chemistry
Surface Properties
TOR protein
TOR Serine-Threonine Kinases - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Specifically designed and functionalized nanoparticles hold great promise for biomedical applications. Yet, the applicability of nanoparticles is critically predetermined by their surface functionalization and biodegradability. Here we demonstrate that amino-functionalized polystyrene nanoparticles (PS-NH ), but not amino- or hydroxyl-functionalized silica particles, trigger cell death in hepatocellular carcinoma Huh7 cells. Importantly, biodegradability of nanoparticles plays a crucial role in regulation of essential cellular processes. Thus, biodegradable silica nanoparticles having the same shape, size and surface functionalization showed opposite cellular effects in comparison with similar polystyrene nanoparticles. At the molecular level, PS-NH obstruct and amino-functionalized silica nanoparticles (Si-NH ) activate the mTOR signalling in Huh7 and HepG2 cells. PS-NH induced time-dependent lysosomal destabilization associated with damage of the mitochondrial membrane. Solely in PS-NH -treated cells, permeabilization of lysosomes preceded cell death. Contrary, Si-NH nanoparticles enhanced proliferation of HuH7 and HepG2 cells. Our findings demonstrate complex cellular responses to functionalized nanoparticles and suggest that nanoparticles can be used to control activation of mTOR signaling with subsequent influence on proliferation and viability of HuH7 cells. The data provide fundamental knowledge which could help in developing safe and efficient nano-therapeutics.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-16447-6