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

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


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دانشگاه علوم پزشکی تبریز
دانشگاه علوم پزشکی تبریز

نویسندگان: فرهاد جدیدی نیارق , علی مسجدی

کلمات کلیدی: A2AR; Adenosine; Breast cancer; Nanoparticle; T cells; siRNA

نشریه: 15718 , 1 , 133 , 2019

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نویسنده ثبت کننده مقاله فرهاد جدیدی نیارق
مرحله جاری مقاله تایید نهایی
دانشکده/مرکز مربوطه مرکز تحقیقات ایمونولوژی
کد مقاله 66314
عنوان فارسی مقاله 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
عنوان لاتین مقاله 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
ناشر 12
آیا مقاله از طرح تحقیقاتی و یا منتورشیپ استخراج شده است؟ خیر
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نوع مقاله Original Article
نحوه ایندکس شدن مقاله ایندکس شده سطح یک – ISI - Web of Science
آدرس لینک مقاله/ همایش در شبکه اینترنت

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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).

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نویسنده نفر چندم مقاله
فرهاد جدیدی نیارقدوازدهم
علی مسجدیاول

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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..pdf1398/02/182777891دانلود