T-cell activation by antigen-loaded pH-sensitive hydrogel particles in vivo: the effect of particle size.
T-cell activation by antigen-loaded pH-sensitive hydrogel particles in vivo: the effect of particle size.
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DOI：
10.1021/bc800338n
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发表时间：
2009-01
影响因子：
4.7
通讯作者：
Frechet, Jean M. J.
中科院分区：
文献类型：
--
作者：
Cohen, Joel A.;Beaudette, Tristan T.;Tseng, William W.;Bachelder, Eric M.;Mende, Ines;Engleman, Edgar G.;Frechet, Jean M. J.
蛋白质抗原的聚合载体在提高疫苗和免疫疗法对癌症等疾病的疗效方面具有巨大的潜力。我们最近开发了一种基于聚丙烯酰胺水凝胶微粒与酸不稳定部分交联的载体体系。在被抗原呈递细胞吞噬后，包裹在载体内的蛋白质被释放出来，并为随后的抗原表位呈递进行加工。为了了解颗粒大小对抗原提呈细胞摄取后t细胞活化的影响，采用乳液和微乳液聚合技术分别合成了平均直径为3.5 μm和35 nm的包裹模型蛋白抗原的颗粒。体内试验表明，两种大小的颗粒都能有效地刺激t细胞的增殖，并且当与免疫刺激性DNA共同施用时，能够产生抗原特异性的细胞毒性t细胞反应。与之前的文献报道相反，我们的结果表明，在这些实验中使用的两种大小的颗粒，t细胞的激活程度没有显著差异。这些发现的差异可能与这些研究中使用的载体材料性质的根本差异有关，例如这里描述的聚丙烯酰胺颗粒的亲水性与其他研究小组研究的载体的疏水性。
Polymeric carriers of protein antigens have great potential for improving the efficacy of vaccines and immunotherapeutics for diseases such as cancer. We recently developed a carrier system based on polyacrylamide hydrogel microparticles crosslinked with acid-labile moieties. After being phagocytosed by antigen-presenting cells, the protein encapsulated within the carrier is released and processed for subsequent presentation of antigenic epitopes. To understand the impact of particle size on the activation of T-cells following uptake by antigen-presenting cells, particles with mean diameters of 3.5 μm and 35 nm encapsulating a model protein antigen were synthesized by emulsion and microemulsion based polymerization techniques, respectively. In vivo tests demonstrated that both sizes of particles were effective at stimulating the proliferation of T-cells, and were capable of generating an antigen specific cytotoxic T-cell response when co-administered with immunostimulatory DNA. Contrary to previous reports in the literature, our results suggest that there is no significant difference in the magnitude of T-cell activation for the two sizes of particles used in these experiments. This disparity in findings may be related to fundamental differences in material properties of the carriers used in these studies, such as the hydrophilicity of the polyacrylamide particles described here versus the hydrophobic nature of carriers investigated by other groups.
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影响因子：
10.8
作者：
Reddy, ST;Rehor, A;Swartz, MA
通讯作者：
Swartz, MA
DOI：
10.1073/pnas.0930644100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Murthy, N;Xu, MC;Fréchet, JMJ
通讯作者：
Fréchet, JMJ
影响因子：
4.7
作者：
Cohen, Jessica L.;Almutairi, Adah;Frechet, Jean M. J.
通讯作者：
Frechet, Jean M. J.
影响因子：
4.7
作者：
Standley, Stephany M.;Mende, Ines;Frechet, Jean M. J.
通讯作者：
Frechet, Jean M. J.
影响因子：
32.4
作者：
Randolph, GJ;Inaba, K;Muller, WA
通讯作者：
Muller, WA