A poly(beta-amino ester) activates macrophages independent of NF-κB signaling.
A poly(beta-amino ester) activates macrophages independent of NF-κB signaling.
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DOI：
10.1016/j.actbio.2017.12.040
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发表时间：
2018-03-01
影响因子：
9.7
通讯作者：
Jewell CM
中科院分区：
文献类型：
--
作者：
Dold NM;Zeng Q;Zeng X;Jewell CM
核酸递送媒介物准备在递送用于疫苗和免疫疗法的基因疗法中以及在递送基于核酸的佐剂中发挥重要作用。用于核酸递送的许多常见聚合物递送载体最近已显示与免疫细胞相互作用并直接刺激免疫原性应答，特别是以颗粒形式。聚（β-氨基酯）被设计用于核酸递送，并且已经在许多疫苗和治疗研究中证明了有希望的性能。然而，很少有工作表征这些聚合物激活免疫细胞的机制。在这里，我们证明了聚（β-氨基酯）激活抗原呈递细胞的可溶性和颗粒形式，这些效果是独立的TLR信号通路。此外，我们发现聚合物诱导的激活不依赖于NF-κB信号，但激活IRF，一个重要的先天性炎症通路。将聚（β-氨基酯）或其他聚合物载体的物理化学特征与炎症机制联系起来的新知识可以支持利用这些材料的疫苗和免疫疗法的更合理的设计方法。
Nucleic acid delivery vehicles are poised to play an important role in delivering gene therapy for vaccines and immunotherapies, and in delivering nucleic acid based adjuvants. A number of common polymeric delivery vehicles used in nucleic acid delivery have recently been shown to interact with immune cells and directly stimulate immunogenic responses, particularly in particle form. Poly(beta-amino esters) were designed for nucleic acid delivery and have demonstrated promising performance in a number of vaccine and therapeutic studies. Yet, little work has characterized the mechanisms by which these polymers activate immune cells. Here we demonstrate that a poly(beta-amino ester) activates antigen presenting cells in soluble and particulate forms, and that these effects are independent of TLR signaling pathways. Moreover, we show the polymers induce activation independent of NF-κB signaling, but do activate IRF, an important innate inflammatory pathway. New knowledge linking physicochemical features of poly(beta-amino esters) or other polymeric carriers to inflammatory mechanisms could support more rational design approaches for vaccines and immunotherapies harnessing these materials.
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影响因子：
9.7
作者：
Andorko JI;Hess KL;Pineault KG;Jewell CM
通讯作者：
Jewell CM
影响因子：
4.9
作者：
Andorko, James I.;Pineault, Kevin G.;Jewell, Christopher M.
通讯作者：
Jewell, Christopher M.
影响因子：
4.6
作者：
Mold M;Shardlow E;Exley C
通讯作者：
Exley C
影响因子：
41.2
作者：
DeMuth PC;Min Y;Huang B;Kramer JA;Miller AD;Barouch DH;Hammond PT;Irvine DJ
通讯作者：
Irvine DJ
影响因子：
4.6
作者：
Li N;Sun J;Benet ZL;Wang Z;Al-Khodor S;John SP;Lin B;Sung MH;Fraser ID
通讯作者：
Fraser ID