Marina Bekić (Avtor), Miloš Vasiljević (Avtor), Dušica Stojanović (Avtor), Vanja Kokol (Avtor), Dušan Mihajlović (Avtor), Dragana Vučević (Avtor), Petar S. Uskoković (Avtor), Miodrag Čolić (Avtor), Sergej Tomić (Avtor)

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:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UM FS - Fakulteta za strojništvo
UDK: 677.46:620.3
COBISS: 117195779 Povezava se bo odprla v novem oknu
ISSN: 1178-2013
Št. ogledov: 10
Št. prenosov: 1
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

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