The relevance of physico-chemical properties and protein corona for evaluation of nanoparticles immunotoxicity—in vitro correlation analysis on THP-1 macrophages
ID Pavlin, Mojca (Author), ID Lojk, Jasna (Author), ID Strojan, Klemen (Author), ID Hafner Bratkovič, Iva (Author), ID Jerala, Roman (Author), ID Leonardi, Adrijana (Author), ID Križaj, Igor (Author), ID Drnovšek, Nataša (Author), ID Novak, Saša (Author), ID Veranič, Peter (Author), ID Bregar, Vladimir Boštjan (Author)

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Alongside physiochemical properties (PCP), it has been suggested that the protein corona of nanoparticles (NPs) plays a crucial role in the response of immune cells to NPs. However, due to the great variety of NPs, target cells, and exposure protocols, there is still no clear relationship between PCP, protein corona composition, and the immunotoxicity of NPs. In this study, we correlated PCP and the protein corona composition of NPs to the THP-1 macrophage response, focusing on selected toxicological endpoints: cell viability, reactive oxygen species (ROS), and cytokine secretion. We analyzed seven commonly used engineered NPs (SiO$_2$, silver, and TiO$_2$) and magnetic NPs. We show that with the exception of silver NPs, all of the tested TiO$_2$ types and SiO$_2$ exhibited moderate toxicities and a transient inflammatory response that was observed as an increase in ROS, IL-8, and/or IL-1β cytokine secretion. We observed a strong correlation between the size of the NPs in media and IL-1β secretion. The induction of IL-1β secretion was completely blunted in NLR family pyrin domain containing 3 (NLRP3) knockout THP-1 cells, indicating activation of the inflammasome. The correlations analysis also implicated the association of specific NP corona proteins with the induction of cytokine secretion. This study provides new insights toward a better understanding of the relationships between PCP, protein corona, and the inflammatory response of macrophages for different engineered NPs, to which we are exposed on a daily basis.

Keywords:physico-chemical properties, nanoparticles, nanotoxicology, immune response, correlation, protein corona, cytokines, inflammasome, macrophages, TiO$_2$
Work type:Article
Typology:1.01 - Original Scientific Article
Organization:MF - Faculty of Medicine
FE - Faculty of Electrical Engineering
Publication status:Published
Publication version:Version of Record
Number of pages:23 str.
Numbering:Vol. 23, iss. 11, art. 6197
PID:20.500.12556/RUL-145243 This link opens in a new window
ISSN on article:1422-0067
DOI:10.3390/ijms23116197 This link opens in a new window
COBISS.SI-ID:109968387 This link opens in a new window
Publication date in RUL:13.04.2023
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Record is a part of a journal

Title:International journal of molecular sciences
Shortened title:Int. j. mol. sci.
COBISS.SI-ID:2779162 This link opens in a new window


License:CC BY 4.0, Creative Commons Attribution 4.0 International
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

Keywords:fizikalno-kemijske lastnosti, nanodelci, nanotoksikologija, imunski odziv, korelacija, proteinska korona, citokini, inflamasom, makrofagi, TiO$_2$


Funder:ARRS - Slovenian Research Agency
Project number:J7-7424
Name:Analiza možnih škodljivih učinkov nanodelcev in spremljajočih mehanizmov - od fizikalno-kemijske ter in vitro karakterizacije do aktivacije prirojenega imunskega sistema

Funder:ARRS - Slovenian Research Agency
Project number:J2-6758
Name:Razvoj in in vitro karakterizacija multimodalnih magnetnih nanodelcev za dostavo učinkovin in označevanje celic

Funder:ARRS - Slovenian Research Agency
Project number:J3-1746
Name:Vloga celične smrti v različnih aktivacijskih poteh inflamasoma NLRP3 in njena uporaba za inovativno imunoterapijo raka

Funder:ARRS - Slovenian Research Agency
Project number:J3-6794
Name:Celična energijska presnova kot tarča za zdravljenje raka – genski in farmakološki pristop

Funder:ARRS - Slovenian Research Agency
Project number:J3-7494
Name:Tunelske membranske nanocevke za inovativno zdravljenje raka sečnega mehurja

Funder:ARRS - Slovenian Research Agency
Project number:Z4-8229
Name:Vpliv različnih tipov nanodelcev na živčne celice in makrofage - analiza kratkoročnih in dolgoročnih posledic na celični stres, diferenciacijo in celično signaliziranje

Funder:ARRS - Slovenian Research Agency
Project number:P1-0055
Name:Biofizika polimerov, membran, gelov, koloidov in celic

Funder:ARRS - Slovenian Research Agency
Project number:P3-0108
Name:Diferenciacija urotelijskih celic

Funder:ARRS - Slovenian Research Agency
Project number:P1-0207
Name:Toksini in biomembrane

Funder:ARRS - Slovenian Research Agency
Project number:P4-0220
Name:Primerjalna genomika in genomska biodiverziteta

Funder:ARRS - Slovenian Research Agency
Project number:P2-0087
Name:Keramični in komplementarni materiali za napredne inženirske in biomedicinske aplikacije

Funder:ARRS - Slovenian Research Agency
Project number:P4-0176
Name:Sintezna biologija in imunologija

Funder:ARRS - Slovenian Research Agency
Funding programme:Young researchers

Funder:ARRS - Slovenian Research Agency
Project number:I0-0022
Name:Mreža raziskovalnih infrastrukturnih centrov Univerze v Ljubljani (MRIC UL)

Funder:EC - European Commission
Funding programme:FP7
Project number:621329
Name:ERA Chair for isotope techniques in food quality, safety and traceability

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