The article entitled “Small variations in nanoparticle structure dictate differential cellular stress responses and mode of cell death”, just published in Nanotoxicology, describes details about the toxic mechanisms obtained by testing three very similar nanoparticles on six cancer cell lines. The three different types of particles where all of the class poly(alkylcyanoacrylate), they differed only in their alkyl side chains being butyl (PBCA), ethylbutyl (PEBCA) or octyl (POCA). Such substances have for many years been used as medical glue. The authors describe different effects of these nanoparticles.
In general, the POCA particles were most toxic; they induced endoplasmic reticulum stress and apoptosis. In contrast PBCA and PEBCA particles induced oxidative stress and lipid peroxidation depending on the level of the glutathione precursor cystine and transcription of the cystine transporter SLC7A11. The latter was induced as a protective response by the transcription factors ATF4 and Nrf2, involving different mechanisms for PBCA and PEBCA.
Intriguingly, PBCA particles activated the cell death mechanism ferroptosis, which is a promising option for targeting multi-drug resistant cancers. These findings highlight that even minor differences in nanoparticle composition can severely impact the cellular responses to such particles. Thus, these results may have important implications for selection of nanoparticles for clinical use.
Maria Torgersen is the senior author of this article published in Nanotoxicology with Marzena Szwed and Tonje Sønstevold being shared first authors. Torgersen is a project leader in the group of Kirsten Sandvig at the Department of Molecular Cell Biology.
The particles used in the present study were made by SINTEF Trondheim as part of the five year national competence building project in nanomedicine headed by Sandvig.
The article in Nanotoxicology:
Small variations in nanoparticle structure dictate differential cellular stress responses and mode of cell death.
Szwed M, Sønstevold T, Øverbye A, Engedal N, Grallert B, Mørch Ý, Sulheim E, Iversen TG, Skotland T, Sandvig K, Torgersen ML.
Nanotoxicology. 2019 Feb 14:1-22. doi: 10.1080/17435390.2019.1576238.
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