Microparticle surface modifications targeting dendritic cells for non-activating applications.
Microparticle surface modifications targeting dendritic cells for non-activating applications.
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DOI：
10.1016/j.biomaterials.2012.06.049
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发表时间：
2012-10
期刊：
影响因子：
14
通讯作者：
Keselowsky, Benjamin G.
中科院分区：
文献类型：
--
作者：
Lewis, Jamal S.;Zaveri, Toral D.;Crooks, Charles P., II;Keselowsky, Benjamin G.
将治疗药物输送到DC进行免疫治疗的微粒系统最近受到了关注。然而，关于DC靶向微粒输送系统的优化的报道有限，特别是在目标是以非激活方式向DC输送有效载荷的情况下。在这里，我们研究了以非刺激性方式使用聚(D-丙交酯-乙交酯)微粒(MPS)靶向DC，并评估了体外和体内的疗效。我们通过表面固定DC受体靶向分子-抗体(抗CD11c，抗DEC-205)或多肽(P-D2，RGD)来修饰MPS，其中抗CD11c抗体，P-D2和RGD多肽靶向整合素，抗DEC-205抗体靶向C型凝集素受体DEC-205。结果表明，修饰后的MPS既无毒性也无激活作用，抗DEC-205抗体、抗CD11c抗体和P-D2多肽修饰可提高MPS对DC的体外摄取。P-D2多肽MP修饰显著改善了DC抗原在即刻和延迟时间点的体外提呈。值得注意的是，P-D2肽和抗CD11c抗体对MP的功能化增加了DC和MΦS体内MP转位的速度和程度，其中P-D2肽修饰的MPS转位最高。这项工作为非激活聚合物微粒应用的设计提供了信息，例如用于自身免疫性疾病的疫苗。
Microparticulate systems for delivery of therapeutics to DCs for immunotherapy have gained attention recently. However, reports addressing the optimization of DC-targeting microparticle delivery systems are limited, particularly for cases where the goal is to deliver payload to DCs in a non-activating fashion. Here, we investigate targeting DCs using poly (d lactide-co-glycolide) microparticles (MPs) in a non-stimulatory manner and assess efficacy in vitro and in vivo. We modified MPs by surface immobilizing DC receptor targeting molecules – antibodies (anti-CD11c, anti-DEC-205) or peptides (P-D2, RGD), where anti-CD11c antibody, P-D2 and RGD peptides target integrins and anti-DEC-205 antibody targets the c-type lectin receptor DEC-205. Our results demonstrate the modified MPs are neither toxic nor activating, and DC uptake of MPs in vitro is improved by the anti-DEC-205 antibody, the anti-CD11c antibody and the P-D2 peptide modifications. The P-D2 peptide MP modification significantly improved DC antigen presentation in vitro both at immediate and delayed time points. Notably, MP functionalization with P-D2 peptide and anti-CD11c antibody increased the rate and extent of MP translocation in vivo by DCs and MΦs, with the P-D2 peptide modified MPs demonstrating the highest translocation. This work informs the design of non-activating polymeric microparticulate applications such as vaccines for autoimmune diseases.
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影响因子：
15.3
作者：
Bonifaz, L;Bonnyay, D;Mahnke, K;Rivera, M;Nussenzweig, MC;Steinman, RM
通讯作者：
Steinman, RM
影响因子：
9.7
作者：
Acharya, Abhinav P.;Dolgova, Natalia V.;Keselowsky, Benjamin G.
通讯作者：
Keselowsky, Benjamin G.
影响因子：
14
作者：
Acharya, Abhinav P.;Clare-Salzler, Michael J.;Keselowsky, Benjamin G.
通讯作者：
Keselowsky, Benjamin G.
影响因子：
2.7
作者：
Gogolák, P;Réthi, B;Rajnavölgyi, É
通讯作者：
Rajnavölgyi, É
影响因子：
6.4
作者：
Ammon, C;Meyer, SP;Kreutz, M
通讯作者：
Kreutz, M