Phosphonate-Modified Cellulose Nanocrystals Potentiate the Th1 Polarising Capacity of Monocyte-Derived Dendritic Cells via GABA-B Receptor

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dc.citation.epage3216
dc.citation.spage3191
dc.citation.volume17
dc.contributor.authorBekić, Marina
dc.contributor.authorVasiljević, Miloš
dc.contributor.authorStojanović, Dušica
dc.contributor.authorKokol, Vanja
dc.contributor.authorMihajlović, Dušan
dc.contributor.authorVučević, Dragana
dc.contributor.authorUskoković, Petar
dc.contributor.authorČolić, Miodrag
dc.contributor.authorTomić, Sergej
dc.date.accessioned2023-05-19T12:25:55Z
dc.date.available2023-05-19T12:25:55Z
dc.date.issued2022
dc.description.abstractPurpose: 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.
dc.identifier.doi10.2147/IJN.S362038
dc.identifier.urihttps://vaseljena.ues.rs.ba/handle/123456789/178
dc.language.isoen
dc.publisherDove Medical Press
dc.sourceInternational Journal of Nanomedicine
dc.subjectcellulose nanocrystals, phosphonates, dendritic cells, immunomodulation, GABA-B receptor
dc.titlePhosphonate-Modified Cellulose Nanocrystals Potentiate the Th1 Polarising Capacity of Monocyte-Derived Dendritic Cells via GABA-B Receptor
dc.typeArticle
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