Naslov (eng)

Cellulose Nanocrystals as a Versatile Platform for Regulation of Myeloid Cell Immunogenicity

Autor

Tomić, Sergej
Kokol, Vanja
Čolić, Miodrag
Uskoković, Petar
Vučević, Dragana
Stojanović, Dušica
Vasiljević, Miloš
Bekić, Marina

Publisher

Opis (eng)

ABSTRACT Phosphonates possess a great potential for the therapy of bone tumours due to their inhibitory potential for osteoclasts. The delivery of phosphonates via cellulose nanocrystals (CNCs) seems a promising approach for their increased efficacy in target tissues. However, the immunological effects of these conjugates have not been investigated thoroughly. Here we modified used wood-based native (n)CNC, oxidized (ox-CNC) and phosphonate (3 AminoPropylphosphonic Acid (ApA))-conjugated CNC to test their physicochemical properties and immunomodulatory potential. Modification of CNC increased their elasticity module and hardness, which resulted in their reduced internalization by phagocytic cells. The non-toxic doses of native and modified CNC displayed different immunomodulatory properties in models of human peripheral blood mononuclear cells (PBMCs) and monocyte-derived dendritic cells (moDCs). Namely, nCNC displayed a tolerogenic potential upon internalization by MoDCs, as judged by their capacity to up-regulate IDO-1, PDL1, ILT3 and IL27 expression, and potentiate their capacity to induce FoxP3+ regulatory T cells when present during the differentiation of monocytes into MoDCs. These properties make nCNC promising in the treatment of chronic inflammatory diseases such as autoimmunity and transplantation. In contrast, ApA-CNC induced oxidative stress and autophagy in MoDCs and up-regulated maturation markers on MoDCs, including CD83, CD86, NLRP3, IL-1β and IL-12 production. Consequently, ApA-CNC-treated MoDCs displayed an increased allostimulatory potential and Th1/CTL polarizing activity in co-cultures with T cells. We found that the stimulatory effects of ApA-CNC on MoDCs were mediated via GABA-B receptor and down-regulation of cAMP levels in MoDCs, as the blockage of the receptor diminished the effects of ApA-CNC. Moreover, the Th1 polarizing and allostimulatory capacity of MoDCs differentiated with ApA-CNC were preserved upon LPS and IFN-γ treatment, which correlated with late expression of R2 subunit of GABA-B receptor during MoDCs differentiation. Therefore, the delivery of ApA via CNC induces potent DC-mediated Th1 polarization which could be harnessed for development new treatment of bone malignancies. This research was supported by the Ministry of Education, Science and Technological Development (Contract No. 451- 03-68/2020-14/ 200020) and the Science Fund of the Republic of Serbia (PROMIS, #6062673, Nano-MDSC-Thera).

Jezik

engleski

Datum

2022

Licenca

Ovo delo je licencirano pod uslovima licence
Creative Commons CC BY-NC-ND 4.0 - Creative Commons Autorstvo - Nekomercijalno - Bez prerada 4.0 International License.

http://creativecommons.org/licenses/by-nc-nd/4.0/legalcode

Deo kolekcije (1)

o:25140

Radovi Instituta za primenu nuklearne energije - INEP