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

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

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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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