Targeted antigen delivery to dendritic cell via functionalized alginate nanoparticles for cancer immunotherapy
Targeted antigen delivery to dendritic cell via functionalized alginate nanoparticles for cancer immunotherapy
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DOI：
10.1016/j.jconrel.2017.04.020
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发表时间：
2017-06
影响因子：
10.8
通讯作者：
Chuangnian Zhang;Gaona Shi;Ju Zhang;Huijuan Song;Jinfeng Niu;S. Shi;Pingsheng Huang;Yanming Wang-Yanming
中科院分区：
文献类型：
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作者：
Chuangnian Zhang;Gaona Shi;Ju Zhang;Huijuan Song;Jinfeng Niu;S. Shi;Pingsheng Huang;Yanming Wang-Yanming
本研究的目的是确定一种“易于采用”的策略，以增强免疫反应，使用功能化的海藻酸盐（ALG）纳米粒子（MAN-ALG/ALG=OVA NPs），这是由CaCl 2交联的两种不同类型的ALG制备。甘露糖（MAN）修饰的ALG（MAN-ALG）用于树突状细胞靶向。另一组分由模型抗原卵清蛋白（OVA）组成，通过pH敏感的Schiff碱键与ALG（ALG=OVA）缀合。FT-IR和1H NMR表征了海藻酸钠的接枝，TEM和DLS表征了MAN-ALG/ALG=OVA纳米粒的形貌、粒径和Zeta电位。用流式细胞仪和激光共聚焦显微镜观察MAN-ALG/ALG= OVANPs对体外培养的小鼠骨髓树突状细胞（BMDCs）的抗原摄取。结果显示MAN-ALG/ALG=OVA纳米粒促进BMDCs的抗原摄取和抗原的胞浆释放。与游离OVA相比，MAN-ALG/ALG=OVA NPs处理的BMDCs细胞因子分泌和表面共刺激分子的表达水平也显著上调。使用Cy 7（一种近红外荧光染料）标记的MAN-ALG/ALG=OVA NPs进行的体内分布研究表明，MAN-ALG/ALG=OVA NPs有效地将纳米颗粒从注射部位运输到引流淋巴结。此外，发现MAN-ALG/ALG=OVA NPs体外增强OVA对B3 Z T细胞杂交结构域的交叉呈递。皮下施用MAN-ALG/ALG=OVA NP还诱导C57 BL/6小鼠中主要的细胞毒性T淋巴细胞（CTL）应答和E.G7肿瘤生长的抑制。总之，我们在此报告MAN-ALG/ALG=OVA NP具有作为用于癌症免疫治疗的有效纳米疫苗的潜力。
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 CaCl2cross-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 and1H 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 microscopyin vitrousing 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 vivobio-distribution study using Cy7 (a near-infrared fluorescence dye) labeled MAN-ALG/ALG=OVA NPs showed efficientin vivotrafficking 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 hybridomain 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.