Nanodiamonds (NDs) display several attractive features rendering them useful for medical applications such as drug delivery. However, the interactions between NDs and the immune system remain poorly understood. Here, we investigated amino-, carboxyl-, and poly(ethylene glycol) (PEG)-terminated NDs with respect to primary human immune cells. We applied cytometry by time-of-flight (CyToF) to assess the impact on peripheral blood mononuclear cells at the single-cell level, and observed an expansion of plasmacytoid dendritic cells (pDCs) which are critically involved in antiviral responses. Subsequent experiments demonstrated that the NDs were actively internalized, leading to a vigorous type I interferon response involving endosomal Toll-like receptors. ND-NH2 and ND-COOH were more potent than ND-PEG, as evidenced by using TLR reporter cell lines. Computational studies demonstrated that NDs interacted with the ligand-binding domains of TLR7 and TLR9 with high affinity though this was less pronounced for ND-PEG. NDs with varying surface functionalities were also readily taken up by macrophages. To gain further insight, we performed RNA sequencing of a monocyte-like cell line exposed to NDs, and found that the phagosome maturation pathway was significantly affected. Indeed, evidence for lysosomal hyperacidification was obtained in dendritic cells and macrophages exposed to NDs. Moreover, using a reporter cell line, NDs were found to impinge on autophagic flux. However, NDs did not affect viability of any of the cell types studied. This study has shown that NDs subvert dendritic cells leading to an antiviral-like immune response. This has implications not only for drug delivery but also for anticancer vaccines using NDs.

• Klíčová slova
• autophagy, dendritic cells, interferon, macrophages, nanodiamonds,
• MeSH
• dendritické buňky * účinky léků   imunologie   MeSH
• endozomy MeSH
• interferon typ I * imunologie   MeSH
• lidé MeSH
• lyzozomy MeSH
• makrofágy * účinky léků   imunologie   MeSH
• myši MeSH
• nanodiamanty * MeSH
• polyethylenglykoly MeSH
• RAW 264.7 buňky MeSH
• THP-1 buňky MeSH
• toll-like receptory imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• interferon typ I * MeSH
• nanodiamanty * MeSH
• polyethylenglykoly MeSH
• toll-like receptory MeSH

Carbon-based nanomaterials (C-BNM) have recently attracted an increased attention as the materials with potential applications in industry and medicine. Bioresistance and proinflammatory potential of C-BNM is the main obstacle for their medicinal application which was documented in vivo and in vitro. However, there are still limited data especially on graphene derivatives such as graphene platelets (GP). In this work, we compared multi-walled carbon nanotubes (MWCNT) and two different types of pristine GP in their potential to activate inflammasome NLRP3 (The nod-like receptor family pyrin domain containing 3) in vitro. Our study is focused on exposure of THP-1/THP1-null cells and peripheral blood monocytes to C-BNM as representative models of canonical and alternative pathways, respectively. Although all nanomaterials were extensively accumulated in the cytoplasm, increasing doses of all C-BNM did not lead to cell death. We observed direct activation of NLRP3 via destabilization of lysosomes and release of cathepsin B into cytoplasm only in the case of MWCNTs. Direct activation of NLRP3 by both GP was statistically insignificant but could be induced by synergic action with muramyl dipeptide (MDP), as a representative molecule of the family of pathogen-associated molecular patterns (PAMPs). This study demonstrates a possible proinflammatory potential of GP and MWCNT acting through NLRP3 activation.

• Klíčová slova
• THP-1, carbon nanotubes, cathepsin B, graphene platelets, inflammasome NLRP3, macrophages,
• Publikační typ
• časopisecké články MeSH

This study provides a review of the therapeutic potential of graphene dressing scaffolds and mesenchymal stem cells (MSCs) and their synergistic effects with respect to cutaneous wound healing. This study also considers their putative action mechanism based on the antibacterial, immunomodulating, angiogenic, matrix remodeling effects of materials belonging to the graphene family and MSCs during the wound healing process. In addition, this study discusses the cytocompatibility of graphene, its uses as a platform for skin substitutes, the properties it possesses with respect to providing protection against microbial invasion as well as strategies aimed at minimizing the chance of the occurrence of sepsis. MSCs are capable of secreting several factors that exert a therapeutic impact on reparative processes and tissue regeneration. In light of experiments conducted to date, graphene combined with MSCs appears to have the potential to enhance both the wound healing process and infection control at the injury site.

• Klíčová slova
• graphene, healing, mesenchymal stem cells, wound,
• MeSH
• grafit chemie   farmakologie   MeSH
• hojení ran účinky léků   MeSH
• imunomodulace účinky léků   MeSH
• kůže účinky léků   zranění   patologie   MeSH
• lidé MeSH
• mezenchymální kmenové buňky cytologie   účinky léků   MeSH
• transplantace mezenchymálních kmenových buněk * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• grafit MeSH