Masjedi, A and Hassannia, H and Atyabi, F and Rastegari, A and Hojjat-Farsangi, M and Namdar, A and Soleimanpour, H and Azizi, G and Nikkhoo, A and Ghalamfarsa, G and Mirshafiey, A and Jadidi-Niaragh, F (2019) Downregulation of A2AR by siRNA loaded PEG-chitosan-lactate nanoparticles restores the T cell mediated anti-tumor responses through blockage of PKA/CREB signaling pathway. International Journal of Biological Macromolecules, 133. pp. 436-445. ISSN 01418130
Full text not available from this repository.Abstract
Adenosine and its receptors are novel promising targets for cancer immunotherapy. In here, we aimed to evaluate the efficacy of Polyethylene glycol (PEG)-chitosan-lactate (PCL) nanoparticles (NPs) loaded with A2AR-specific siRNA for interfering with differentiation and function of T cells derived from the 4T1 breast tumor-bearing Balb/C mice, ex vivo. The size of synthesized NPs was about 100 nm in association with low polydispersive index (pdi < 0.3) and a zeta potential of 11 mV. In association with good physicochemical characteristics, NPs exhibited high transfection efficiency in T cells and low toxicity on the various cell lines. T cells were treated with A2AR siRNA-loaded NPs demonstrated suppressed expression of A2AR which was associated with increased proliferation, reduced apoptosis, increased production of inflammatory and reduced secretion of inhibitory cytokines compared to untreated T cells. Moreover, differentiation of conventional T cells purified from tumor-bearing mice to regulatory T cells (Treg) was blocked using A2AR-specific siRNA-loaded NPs. These immune-stimulatory effects were in part through downregulation of protein kinase A/cAMP-response element binding protein (PKA/CREB) axis and upregulation of nuclear factor-κB (NF-κB).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | A2AR،Adenosine،Breast cancer،Nanoparticle،siRNA،T cells |
| Subjects: | QZ Pathology |
| Divisions: | Research Center > Persian Gulf Marine Biotechnology Research Center |
| Depositing User: | خدیجه شبانکاره |
| Date Deposited: | 30 Dec 2020 06:33 |
| Last Modified: | 30 Dec 2020 06:33 |
| URI: | http://eprints.bpums.ac.ir/id/eprint/9210 |
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