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首页> 外文期刊>Advanced Functional Materials >Immune Complexes Mimicking Synthetic Vaccine Nanoparticles for Enhanced Migration and Cross-Presentation of Dendritic Cells
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Immune Complexes Mimicking Synthetic Vaccine Nanoparticles for Enhanced Migration and Cross-Presentation of Dendritic Cells

机译：模仿合成疫苗纳米粒子的免疫复合物，可增强树突状细胞的迁移和交叉表达。

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The well-designed activation of dendritic cells (DCs) by enhancing the delivery of antigens and immunostimulatory adjuvants into DCs is a key strategy for efficient cancer immunotherapy. Antigen-antibody immune complexes (ICs) are known to directly bind to and cross-link Fc-gamma receptors (Fc gamma Rs) on DCs, which induce enhanced migration of DCs to draining lymph nodes through the up-regulation of the chemokine receptor CCR7 and cross-presentation inducing cytotoxic T lymphocyte (CTL) response against tumor antigen. In this study, ICs mimicking synthetic vaccine nanoparticles (NPs) are designed and synthesized by the coating of poly (lactic-co-glycolic acid) (PLGA) NPs containing adjuvant (CpG oligodeoxynuleotides (ODNs) as toll-like receptor 9 ligands) with ovalbumin (OVA) proteins (as model antigens) and by the formation of OVA-OVA antibody ICs. Through the combination of Fc gamma Rs-mediated efficient antigen uptake and CpG ODNs-based immunostimulation, the secretion of TNF-alpha (12.3-fold), IL-6 (7.29-fold), and IL-12 (11-fold), homing ability to lymph nodes (7.5-fold), and cross-presentation (83.8-fold IL-2 secretion) are dramatically increased in DCs treated with PLGA(IC/CpG) NPs. Furthermore, mice vaccinated with DCs treated with PLGA(IC/CpG) NPs induced significant tumor (EG7-OVA) growth inhibition as well as prolonged survival through CTL-mediated enhanced cytotoxicity, antigen-specific responses, and IFN-gamma secretion.
机译：通过增强抗原和免疫刺激佐剂向DC的传递，精心设计的树突状细胞（DC）激活是有效癌症免疫疗法的关键策略。已知抗原抗体免疫复合物（ICs）直接与DC上的Fc-γ受体（Fc gamma Rs）结合并交联，通过上调趋化因子受体CCR7诱导DC迁移至引流淋巴结的过程增强。和交叉呈递诱导针对肿瘤抗原的细胞毒性T淋巴细胞（CTL）反应。在这项研究中，通过合成包含佐剂（CpG寡脱氧核糖核苷酸（ODN）作为收费型受体9配体）的聚乳酸-乙醇酸（PLGA）NP，设计并合成了模拟合成疫苗纳米颗粒（NP）的IC。卵清蛋白（OVA）蛋白（作为模型抗原）并通过形成OVA-OVA抗体IC。通过FcγRs介导的有效抗原摄取和基于CpG ODNs的免疫刺激的结合，TNF-α（12.3倍），IL-6（7.29倍）和IL-12（11倍）的分泌，在用PLGA（IC / CpG）NP处理的DC中，淋巴结的归巢能力（7.5倍）和交叉呈递（IL-2分泌83.8倍）显着增加。此外，接种用PLGA（IC / CpG）NP处理的DC的小鼠可诱导显着的肿瘤（EG7-OVA）生长抑制，并通过CTL介导的增强的细胞毒性，抗原特异性反应和IFN-γ分泌延长生存期。

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  • 来源
    《Advanced Functional Materials》 |2016年第44期|8072-8082|共11页
  • 作者

    Kim Sun-Young; Phuengkham Hathaichanok; Noh Young-Woock; Lee Hong-Guen; Um Soong Ho; Lim Yong Taik;

  • 作者单位

    Sungkyunkwan Univ, SKKU Adv Inst Nanotechnol SAINT, 2066 Seobu Ro, Suwon 440746, Gyeonggi Do, South Korea;

    Sungkyunkwan Univ, SKKU Adv Inst Nanotechnol SAINT, 2066 Seobu Ro, Suwon 440746, Gyeonggi Do, South Korea;

    Sungkyunkwan Univ, SKKU Adv Inst Nanotechnol SAINT, 2066 Seobu Ro, Suwon 440746, Gyeonggi Do, South Korea;

    Sungkyunkwan Univ, Sch Chem Engn, 2066 Seobu Ro, Suwon 440746, Gyeonggi Do, South Korea;

    Sungkyunkwan Univ, Sch Chem Engn, 2066 Seobu Ro, Suwon 440746, Gyeonggi Do, South Korea;

    Sungkyunkwan Univ, SKKU Adv Inst Nanotechnol SAINT, 2066 Seobu Ro, Suwon 440746, Gyeonggi Do, South Korea|Sungkyunkwan Univ, Sch Chem Engn, 2066 Seobu Ro, Suwon 440746, Gyeonggi Do, South Korea;

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