Enhanced antigen presentation and immunostimulation of dendritic cells using acid-degradable cationic nanoparticles.
Enhanced antigen presentation and immunostimulation of dendritic cells using acid-degradable cationic nanoparticles.
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DOI：
10.1016/j.jconrel.2005.02.027
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发表时间：
2005-07-20
期刊：
影响因子：
--
通讯作者：
Fréchet JM
中科院分区：
文献类型：
--
作者：
Kwon YJ;Standley SM;Goh SL;Fréchet JM
以酸可裂解缩醛为交联剂，采用反相微乳液聚合法制备了包埋模型抗原(即卵清蛋白)的酸可降解阳离子纳米粒子。将这些可降解的纳米颗粒与来自骨髓的树突状细胞(BMDCs)孵育，可以增强卵清蛋白衍生的多肽的提呈，正如CD8+T细胞杂交瘤B3Z细胞所定量的那样。颗粒的阳离子性质导致了BMDCs表面吞噬作用的增加，这是成功传递抗原所要克服的第一个障碍。这些颗粒的酸敏感性引导更多的卵蛋白抗原被加工成适当修剪的多肽片段，并在酸性溶酶体内水解后通过主要组织相容性复合体(MHC)I类途径呈现。未甲基化的CpG寡核苷酸(CpG ODN)和抗白细胞介素10的寡核苷酸(AS10 ODN)等佐剂分子可以与蛋白抗原共传递，从而获得最大的细胞免疫应答。
Acid-degradable cationic nanoparticles encapsulating a model antigen (i.e., ovalbumin) were prepared by inverse microemulsion polymerization with acid-cleavable acetal cross-linkers. Incubation of these degradable nanoparticles with dendritic cells derived from bone marrow (BMDCs) resulted in the enhanced presentation of ovalbumin-derived peptides, as quantified by B3Z cells, a CD8+ T cell hybridoma. The cationic nature of the particles contributed to the increased surface endocytosis (or phagocytosis) observed with BMDCs, which is the first barrier to overcome for successful antigen delivery. The acid sensitivity of the particles served to direct more ovalbumin antigens to be processed into the appropriately trimmed peptide fragments and presented via the major histocompatibility complex (MHC) class I pathway following hydrolysis within the acidic lysosomes. It was also shown that adjuvant molecules such as unmethylated CpG oligonucleotides (CpG ODN) and anti-interleukin-10 oligonucleotides (AS10 ODN) could be co-delivered with the protein antigen for maximized cellular immune response.
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影响因子：
4.4
作者：
Heit, A;Maurer, T;Wagner, H
通讯作者：
Wagner, H
影响因子：
56.9
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.0930644100
发表时间：
2003-04-29
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
5.5
作者：
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通讯作者：
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