Povzetek
Purpose:
Phosphonates, like 3-AminoPropylphosphonic Acid (ApA), possess a great potential for the therapy of bone tumours, and their delivery via cellulose nanocrystals (CNCs) seems a promising approach for their increased efficacy in target tissues. However, the immunological effects of CNC-phosphonates have not been investigated thoroughly. The main aim was to examine how the modification of CNCs with phosphonate affects their immunomodulatory properties in human cells.
Methods:
Wood-based native (n) CNCs were modified via oxidation (ox-CNCs) and subsequent conjugation with ApA (ApA-CNCs). CNCs were characterised by atomic force microscopy (AFM) and nanoindentation. Cytotoxicity and immunomodulatory potential of CNCs were investigated in cultures of human peripheral blood mononuclear cells (PBMCs) and monocyte-derived dendritic cells (MoDCs)/T cells co-cultures by monitoring phenotype, cytokines production, allostimulatory and Th/Treg polarisation capacity.
Results:
AFM showed an increase in CNCs’ thickens, elasticity modulus and hardness during the modification with ApA. When applied at non-toxic doses, nCNCs showed a tolerogenic potential upon internalisation by MoDCs, as judged by their increased capacity to up-regulate tolerogenic markers and induce regulatory T cells (Treg), especially when present during the differentiation of MoDCs. In contrast, ox- and ApA-CNCs induced oxidative stress and autophagy in MoDCs, which correlated with their stimulatory effect on the maturation of MoDCs, but also inhibition of MoDCs differentiation. ApA-CNC-treated MoDCs displayed the highest allostimulatory and Th1/CTL polarising activity in co-cultures with T cells. These effects of ApA-CNCs were mediated via GABA-B receptor-induced lowering of cAMP levels in MoDCs, and they could be blocked by GABA-B receptor inhibitor. Moreover, the Th1 polarising and allostimulatory capacity of MoDCs differentiated with ApA-CNC were largely preserved upon the maturation of MoDCs, whereas nCNC- and ox-CNC-differentiated MoDCs displayed an increased tolerogenic potential.
Conclusion:
The delivery of ApA via CNCs induces potent DC-mediated Th1 polarisation, which could be beneficial in their potential application in tumour therapy.
Ključne besede
celuloza;celulozni nanokristali;fosfonati;dendritične celice;imunomodulacija;GABA-B receptorji;cellulose nanocrystals;phosphonates;dendritic cells;regulatory T-cell subsets;immunomodulation;GABA-B receptor;
Podatki
Jezik: |
Angleški jezik |
Leto izida: |
2022 |
Tipologija: |
1.01 - Izvirni znanstveni članek |
Organizacija: |
UM FS - Fakulteta za strojništvo |
UDK: |
677.46:620.3 |
COBISS: |
117195779
|
ISSN: |
1178-2013 |
Št. ogledov: |
10 |
Št. prenosov: |
1 |
Ocena: |
0 (0 glasov) |
Metapodatki: |
|
Ostali podatki
Sekundarni jezik: |
Slovenski jezik |
Sekundarne ključne besede: |
celuloza;celulozni nanokristali;fosfonati;dendritične celice;imunomodulacija;GABA-B receptorji; |
Vrsta dela (COBISS): |
Znanstveno delo |
Strani: |
str. 3191-3216 |
Zvezek: |
ǂVol. ǂ17 |
Čas izdaje: |
July 2022 |
DOI: |
10.2147/IJN.S362038 |
ID: |
19814342 |