کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5433770 1508994 2017 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Targeted antigen delivery to dendritic cell via functionalized alginate nanoparticles for cancer immunotherapy
ترجمه فارسی عنوان
تحویل آنتی ژن هدفمند به سلول دندریتیک از طریق نانوذرات آلژینات کارکردی برای ایمونوتراپی سرطان
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
چکیده انگلیسی

The purpose of the present study was to identify an “easy-to-adopt” strategy to enhance immune responses using functionalized alginate (ALG) nanoparticles (MAN-ALG/ALG=OVA NPs), which were prepared by CaCl2 cross-linking of two different types of ALG. The mannose (MAN) modified ALG (MAN-ALG) was used for dendritic cell targeting. The other component, composed of ovalbumin (OVA), a model antigen, is conjugated to ALG (ALG=OVA) via pH sensitive Schiff base bond. Grafting of alginate was demonstrated by FT-IR and 1H NMR, while the morphological structure, particle size, Zeta potential of MAN-ALG/ALG=OVA NPs were measured using TEM and DLS. The OVA releasing behavior of MAN-ALG/ALG=OVA NPs was determined as a function of pH. Antigen uptake was examined by flow cytometry and confocal laser scanning microscopy in vitro using mouse bone marrow dendritic cells (BMDCs). The results showed that MAN-ALG/ALG=OVA NPs facilitated antigen uptake of BMDCs and cytosolic release of the antigen. Significant up-regulation of cytokine secretion and expression levels of the surface co-stimulatory molecules were also observed in MAN-ALG/ALG=OVA NPs-treated BMDCs, compared to free OVA. In vivo bio-distribution study using Cy7 (a near-infrared fluorescence dye) labeled MAN-ALG/ALG=OVA NPs showed efficient in vivo trafficking of the nanoparticles from the injection site to the draining lymph nodes. Moreover, MAN-ALG/ALG=OVA NPs were found to enhance cross-presentation of OVA to B3Z T cell hybridoma in vitro. Subcutaneous administration of MAN-ALG/ALG=OVA NPs also induced major cytotoxic T lymphocytes (CTL) response and inhibition of E.G7 tumor growth in C57BL/6 mice. In summary, we report here that the MAN-ALG/ALG=OVA NPs have the potential as a potent nanovaccine for cancer immunotherapy.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 256, 28 June 2017, Pages 170-181
نویسندگان
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