In vitro analysis of acetalated dextran microparticles as a potent delivery platform for vaccine adjuvants.
In vitro analysis of acetalated dextran microparticles as a potent delivery platform for vaccine adjuvants.
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DOI：
10.1021/mp900311x
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发表时间：
2010-06-07
影响因子：
4.9
通讯作者：
Keane-Myers AM
中科院分区：
文献类型：
--
作者：
Bachelder EM;Beaudette TT;Broaders KE;Fréchet JM;Albrecht MT;Mateczun AJ;Ainslie KM;Pesce JT;Keane-Myers AM
toll样受体（TLR）激动剂可诱导强效先天免疫反应，可用于开发新型疫苗佐剂。然而，如tlr7所示，TLR的进入可能具有挑战性，它位于细胞内的内体区室中。为了增加tlr7的识别和随后的刺激作用，咪喹莫特被包裹在醋酸化葡聚糖（Ac-DEX）微粒中。Ac-DEX是一种水不溶性和生物相容性聚合物，在pH值7.4时相对稳定，但在酸性条件下，如溶酶体囊泡中，会迅速降解。为了确定包封咪喹莫特的免疫刺激能力，我们比较了游离咪喹莫特和包封咪喹莫特在激活RAW 264.7巨噬细胞、h - s巨噬细胞和骨髓源树突状细胞方面的功效。与游离药物相比，包封的咪喹莫特可显著提高巨噬细胞中IL-1β、IL-6和TNF-α细胞因子的表达。此外，与游离药物相比，包封咪喹莫特治疗后，经典巨噬细胞活化标志物（iNOS、PD1-L1和NO）显著增加。此外，骨髓来源的树突状细胞产生的IL-1β、IL-6、IL-12p70和MIP-1α水平显著高于接受游离咪喹莫特的树突状细胞。这些结果表明，将TLR配体包封在Ac-DEX微颗粒内可增加免疫刺激，并与疫苗制剂一起使用时，可能更好地预防疾病。
Toll-like receptor (TLR) agonists induce potent innate immune responses and can be used in the development of novel vaccine adjuvants. However, access to TLRs can be challenging as exemplified by TLR 7, which is located intracellularly in endosomal compartments. To increase recognition and subsequent stimulatory effects of TLR 7, imiquimod was encapsulated in acetalated-dextran (Ac-DEX) microparticles. Ac-DEX, a water-insoluble and biocompatible polymer, is relatively stable at pH 7.4, but degrades rapidly under acidic conditions, such as those found in lysosomal vesicles. To determine the immunostimulatory capacity of encapsulated imiquimod, we compared the efficacy of free versus encapsulated imiquimod in activating RAW 264.7 macrophages, MH-S macrophages, and bone marrow derived dendritic cells. Encapsulated imiquimod significantly increased IL-1β, IL-6, and TNF-α cytokine expression in macrophages relative to the free drug. Furthermore, significant increases were observed in classic macrophage activation markers (iNOS, PD1-L1, and NO) after treatment with encapsulated imiquimod over the free drug. Also, bone marrow derived dendritic cells produced significantly higher levels of IL-1β, IL-6, IL-12p70, and MIP-1α as compared to their counterparts receiving free imiquimod. These results suggest that encapsulation of TLR ligands within Ac-DEX microparticles results in increased immunostimulation and potentially better protection from disease when used in conjunction with vaccine formulations.
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影响因子：
64.8
作者：
Houde, M;Bertholet, S;Desjardins, M
通讯作者：
Desjardins, M
影响因子：
7.3
作者：
Gerster, JF;Lindstrom, KJ;Lupu, M
通讯作者：
Lupu, M
影响因子：
4.3
作者：
Hassan, Ferdaus;Islam, Shamima;Yokochi, Takashi
通讯作者：
Yokochi, Takashi
影响因子：
6.2
作者：
Garulli, Bruno;Castrucci, Maria R.
通讯作者：
Castrucci, Maria R.
DOI：
10.1073/pnas.0901592106
发表时间：
2009-04-07
影响因子：
11.1
作者：
Broaders, Kyle E.;Cohen, Joel A.;Frechet, Jean M. J.
通讯作者：
Frechet, Jean M. J.