In-situ crosslinking hydrogels for combinatorial delivery of chemokines and siRNA-DNA carrying microparticles to dendritic cells.
In-situ crosslinking hydrogels for combinatorial delivery of chemokines and siRNA-DNA carrying microparticles to dendritic cells.
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DOI：
10.1016/j.biomaterials.2009.06.001
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发表时间：
2009-10
期刊：
影响因子：
14
通讯作者：
Roy, Krishnendu
中科院分区：
文献类型：
--
作者：
Singh, Ankur;Suri, Shalu;Roy, Krishnendu
基于聚合物的可注射系统可以以受控的方式同时递送多种生物活性剂，可以显著提高下一代治疗剂的功效。为了使免疫疗法在免疫学上或治疗上都有效，不仅关键的是驱动抗原（Ag）特异性免疫应答强烈地朝向辅助性T细胞1型（Th 1）或Th 2表型，而且关键的是促进在免疫部位募集大量的抗原呈递细胞（APC）。我们最近报道了一个基于微粒的系统，能够同时提供siRNA和DNA的APC。在这里，我们提出了一种原位可交联的，可注射的制剂含有树突状细胞（DC）-化学引诱剂和双模式DNA-siRNA加载的微粒，以吸引未成熟的DC和同时提供，迁移的细胞，免疫调节siRNA和质粒DNA抗原。这些低交联密度水凝胶被设计为在体外2-7天内降解并以持续的方式释放趋化因子。与等效推注剂量相比，携带趋化因子的凝胶在体外持续时间内吸引了4-6倍的DC。有趣的是，迁移的DC能够渗透水凝胶并有效地吞噬携带siRNA/DNA的微粒。水凝胶包埋的微粒共递送白细胞介素-10 siRNA和质粒DNA抗原在体外迁移的原代DC中表现出有效的白细胞介素-10基因敲低。
Polymer-based, injectable systems that can simultaneously deliver multiple bioactive agents in a controlled manner could significantly enhance the efficacy of next generation therapeutics. For immunotherapies to be effective, both prophylactically or therapeutically, it is not only critical to drive the antigen (Ag) specific immune response strongly towards either T helper type 1 (Th1) or Th2 phenotype, but also to promote recruitment of a high number of antigen-presenting cells (APCs) at the site of immunization. We have recently reported a microparticle-based system capable of simultaneously delivering siRNA and DNA to APCs. Here we present an in situ crosslinkable, injectable formulation containing dendritic cell (DC)-chemoattractants and dual-mode DNA-siRNA loaded microparticles to attract immature DCs and simultaneously deliver, to the migrated cells, immunomodulatory siRNA and plasmid DNA antigens. These low crosslink density hydrogels were designed to degrade within 2–7 days in-vitro and released chemokines in a sustained manner. Chemokine carrying gels attracted 4–6 folds more DCs over a sustained period in vitro, compared to an equivalent bolus dose. Interestingly, migrated DCs were able to infiltrate the hydrogels and efficiently phagocytose the siRNA/DNA carrying microparticles. Hydrogel embedded microparticles co-delivering Interleukin-10 siRNA and plasmid DNA antigens exhibited efficient Interleukin-10 gene knockdown in migrated primary DCs in-vitro.
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影响因子：
10.8
作者：
Holland, TA;Tabata, Y;Mikos, AG
通讯作者：
Mikos, AG
影响因子：
10.8
作者：
Kasturi, Sudhir Pai;Qin, Hong;Roy, Krishnendu
通讯作者：
Roy, Krishnendu
影响因子：
10.8
作者：
Hiemstra, Christine;Zhong, Zhiyuan;Feijen, Jan
通讯作者：
Feijen, Jan
影响因子：
14
作者：
Kasturi, SP;Sachaphibulkij, K;Roy, K
通讯作者：
Roy, K
影响因子：
14
作者：
Hori, Yuki;Winans, Amy M.;Irvine, Darrell J.
通讯作者：
Irvine, Darrell J.