Fiche publication
Date publication
septembre 2023
Journal
International journal of pharmaceutics
Auteurs
Membres identifiés du Cancéropôle Est :
Dr CIANFERANI Sarah
,
Dr LEBEAU Luc
,
Mme SCHAEFFER-REISS Christine
,
Pr PONS Françoise
Tous les auteurs :
Arezki Y, Harmouch E, Delalande F, Rapp M, Schaeffer-Reiss C, Galli O, Cianférani S, Lebeau L, Pons F, Ronzani C
Lien Pubmed
Résumé
Carbon dots (CDs) are nanoparticles (NPs) with potential applications in the biomedical field. When in contact with biological fluids, most NPs are covered by a protein corona. As well, upon cell entry, most NP are sequestered in the lysosome. However, the interplay between the lysosome, the protein corona and the biological effects of NPs is still poorly understood. In this context, we investigated the role of the lysosome in the toxicological responses evoked by four cationic CDs exhibiting protonatable or non-protonatable amine groups at their surface, and the associated changes in the CD protein corona. The four CDs accumulated in the lysosome and led to lysosomal swelling, loss of lysosomal integrity, cathepsin B activation, NLRP3 inflammasome activation, and cell death by pyroptosis in a human macrophage model, but with a stronger effect for CDs with titratable amino groups. The protein corona formed around CDs in contact with serum partially dissociates under lysosomal conditions with subsequent protein rearrangement, as assessed by quantitative proteomic analysis. The residual protein corona still contained binding proteins, catalytic proteins, and proteins involved in the proteasome, glycolysis, or PI3k-Akt KEGG pathways, but with again a more pronounced effect for CDs with titratable amino groups. These results demonstrate an interplay between lysosome, protein corona and biological effects of cationic NPs in link with the titratability of NP surface charges.
Mots clés
Carbon dots, Lysosome, Protein corona, Proteomics, Proton sponge effect, Surface charge
Référence
Int J Pharm. 2023 09 6;:123388
