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胺化纳米胶束作为一种定制疫苗佐剂，可触发炎性小体和淋巴结中固有免疫反应的多个分支。

Aminated nanomicelles as a designer vaccine adjuvant to trigger inflammasomes and multiple arms of the innate immune response in lymph nodes.

作者信息

Song Chanyoung, Phuengkham Hathaichanok, Kim Sun-Young, Lee Min Sang, Jeong Ji Hoon, Shin Sung Jae, Lim Yong Taik

机构信息

SKKU Advanced Institute of Nanotechnology, School of Chemical Engineering.

Department of Pharmacy, Sungkyunkwan University, Suwon.

出版信息

Int J Nanomedicine. 2017 Oct 12;12:7501-7517. doi: 10.2147/IJN.S144623. eCollection 2017.

DOI:10.2147/IJN.S144623
PMID:29066896
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5644533/
Abstract

In this study, we suggest a designer vaccine adjuvant that can mimic the drainage of pathogens into lymph nodes and activate innate immune response in lymph nodes. By the amination of multivalent carboxyl groups in poly-(γ-glutamic acid) (γ-PGA) nanomicelles, the size was reduced for rapid entry into lymphatic vessels, and the immunologically inert nanomicelles were turned into potential activators of inflammasomes. Aminated γ-PGA nanomicelles (aPNMs) induced NLRP3 inflammasome activation and the subsequent release of proinflammatory IL-1β. The NLRP3-dependent inflammasome induction mechanism was confirmed through enzyme (cathepsin B and caspase-1) inhibitors and NLRP3 knockout mice model. After the aPNMs were combined with a clinically evaluated TLR3 agonist, polyinosinic-polycytidylic acid sodium salt (aPNM-IC), they triggered multiple arms of the innate immune response, including the secretion of pro-inflammatory cytokines by both inflammasomes and an inflammasome-independent pathway and the included type I interferons.

摘要

在本研究中，我们提出了一种设计型疫苗佐剂，它能够模拟病原体向淋巴结的引流并激活淋巴结中的先天免疫反应。通过对聚（γ-谷氨酸）（γ-PGA）纳米胶束中的多价羧基进行胺化，纳米胶束尺寸减小，以便快速进入淋巴管，原本免疫惰性的纳米胶束转变为炎性小体的潜在激活剂。胺化γ-PGA纳米胶束（aPNMs）诱导NLRP3炎性小体激活以及随后促炎性白细胞介素-1β的释放。通过酶（组织蛋白酶B和半胱天冬酶-1）抑制剂和NLRP3基因敲除小鼠模型证实了NLRP3依赖性炎性小体诱导机制。aPNMs与临床评估的Toll样受体3（TLR3）激动剂聚肌苷酸-聚胞苷酸钠盐（aPNM-IC）结合后，触发了先天免疫反应的多个环节，包括炎性小体和非炎性小体依赖性途径分泌促炎细胞因子以及产生I型干扰素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4726/5644533/10c7bba66e53/ijn-12-7501Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4726/5644533/0eecc84a6d83/ijn-12-7501Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4726/5644533/640628e4c4b8/ijn-12-7501Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4726/5644533/7127d27ce8e7/ijn-12-7501Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4726/5644533/7b0ef3406e8b/ijn-12-7501Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4726/5644533/c4d1efb9bbfd/ijn-12-7501Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4726/5644533/10c7bba66e53/ijn-12-7501Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4726/5644533/0eecc84a6d83/ijn-12-7501Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4726/5644533/640628e4c4b8/ijn-12-7501Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4726/5644533/7127d27ce8e7/ijn-12-7501Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4726/5644533/7b0ef3406e8b/ijn-12-7501Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4726/5644533/c4d1efb9bbfd/ijn-12-7501Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4726/5644533/10c7bba66e53/ijn-12-7501Fig6.jpg

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