TY - JOUR
T1 - Lateral dimension and amino-functionalization on the balance to assess the single-cell toxicity of graphene on fifteen immune cell types
AU - Fusco, Laura
AU - Orecchioni, Marco
AU - Reina, Giacomo
AU - Bordoni, Valentina
AU - Fuoco, Claudia
AU - Gurcan, Cansu
AU - Guo, Shi
AU - Zoccheddu, Martina
AU - Collino, Federica
AU - Zavan, Barbara
AU - Treossi, Emanuele
AU - Yilmazer, Acelya
AU - Palermo, Vincenzo
AU - Bianco, Alberto
AU - Delogu, Lucia Gemma
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/7
Y1 - 2021/7
N2 - Given the wide variety of potential applications of graphene oxide (GO), its consequent release into the environment poses serious concerns on its safety. The future production and exploitation of graphene in the years to come should be guided by its specific chemical-physical characteristics. The unparalleled potential of single-cell mass cytometry (CyTOF) to dissect by high-dimensionality the specific immunological effects of nanomaterials, represents a turning point in nanotoxicology. It helps us to identify the safe graphene in terms of physical-chemical properties and therefore to direct its future safe production. Here we present a high-dimensional study to evaluate two historically indicated as key parameters for the safe exploitation: functionalization and dimension. The role of lateral dimension and the amino-functionalization of GO on their immune impact were here evaluated as synergistic players. To this end, we dissected the effects of GO, characterized by a large or small lateral size (GO 1.32 μm and GO 0.13 μm, respectively), and its amino-functionalized counterpart (GONH2 1.32 μm and GONH2 0.13 μm, respectively) on fifteen cell types of human primary peripheral blood mononuclear cells (PBMCs). We describe how the smallest later size not only evokes pronounced toxicity on the pool of PBMCs compared to larger GOs but also towards the distinct immune cell subpopulations, in particular on non-classical monocytes, plasmacytoid dendritic cells (pDCs), natural killer cells (NKs) and B cells. The amino-functionalization was able to improve the biocompatibility of classical and non-classical monocytes, pDCs, NKs, and B cells. Detailed single-cell analysis further revealed a complex interaction of all GOs with the immune cells, and in particular monocyte subpopulations, with different potency depending on their physicochemical properties. Overall, by high-dimensional profiling, our study demonstrates that the lateral dimension is an important factor modulating immune cells and specifically monocyte activation, but a proper surface functionalization is the dominant characteristic in its immune effects. In particular, the amino-functionalization can critically modify graphene impact dampening the immune cell activation. Our study can serve as a guide for the future broad production and use of graphene in our everyday life.
AB - Given the wide variety of potential applications of graphene oxide (GO), its consequent release into the environment poses serious concerns on its safety. The future production and exploitation of graphene in the years to come should be guided by its specific chemical-physical characteristics. The unparalleled potential of single-cell mass cytometry (CyTOF) to dissect by high-dimensionality the specific immunological effects of nanomaterials, represents a turning point in nanotoxicology. It helps us to identify the safe graphene in terms of physical-chemical properties and therefore to direct its future safe production. Here we present a high-dimensional study to evaluate two historically indicated as key parameters for the safe exploitation: functionalization and dimension. The role of lateral dimension and the amino-functionalization of GO on their immune impact were here evaluated as synergistic players. To this end, we dissected the effects of GO, characterized by a large or small lateral size (GO 1.32 μm and GO 0.13 μm, respectively), and its amino-functionalized counterpart (GONH2 1.32 μm and GONH2 0.13 μm, respectively) on fifteen cell types of human primary peripheral blood mononuclear cells (PBMCs). We describe how the smallest later size not only evokes pronounced toxicity on the pool of PBMCs compared to larger GOs but also towards the distinct immune cell subpopulations, in particular on non-classical monocytes, plasmacytoid dendritic cells (pDCs), natural killer cells (NKs) and B cells. The amino-functionalization was able to improve the biocompatibility of classical and non-classical monocytes, pDCs, NKs, and B cells. Detailed single-cell analysis further revealed a complex interaction of all GOs with the immune cells, and in particular monocyte subpopulations, with different potency depending on their physicochemical properties. Overall, by high-dimensional profiling, our study demonstrates that the lateral dimension is an important factor modulating immune cells and specifically monocyte activation, but a proper surface functionalization is the dominant characteristic in its immune effects. In particular, the amino-functionalization can critically modify graphene impact dampening the immune cell activation. Our study can serve as a guide for the future broad production and use of graphene in our everyday life.
KW - 2D materials
KW - Biocompatibility
KW - Carbon materials
KW - Cytotoxicity
KW - Safety
KW - Single-cell
UR - http://www.scopus.com/inward/record.url?scp=85107968414&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85107968414&partnerID=8YFLogxK
U2 - 10.1016/j.impact.2021.100330
DO - 10.1016/j.impact.2021.100330
M3 - Article
C2 - 35559831
AN - SCOPUS:85107968414
SN - 2452-0748
VL - 23
JO - NanoImpact
JF - NanoImpact
M1 - 100330
ER -