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短双歧杆菌表面层蛋白 B 促进脂质体靶向派氏结中的抗原呈递细胞。

Levilactobacillus brevis surface layer protein B promotes liposome targeting to antigen-presenting cells in Peyer's patches.

机构信息

School of Life Science and Technology, Tokyo Institute of Technology, Japan.

School of Life Science and Technology, Tokyo Institute of Technology, Japan; Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Japan.

出版信息

Int J Pharm. 2022 Jun 25;622:121896. doi: 10.1016/j.ijpharm.2022.121896. Epub 2022 Jun 6.

Abstract

Liposome targeting by conjugation with specific ligands and cross-linking reagents is an attractive strategy for active drug delivery. Here, we demonstrated the potential of surface layer protein (Slp) B from Levilactobacillus brevis JCM 1059 as a specific ligand to antigen-presenting cells (APCs) in Peyer's patches. L. brevis JCM 1059 SlpB-coated liposomes (SlpB-LPs) showed higher resistance to various pH values and bile acids compared to non-coated liposomes (LPs). SlpB-LP showed a significantly higher uptake into dendritic cell-like differentiated THP-1 cells than LP did. The SlpB-LP-conjugated α-galactosylceramide (αGalCer) promoted the production of IL-12 (p40) and TNF-α by THP-1 cells. Furthermore, SlpB-LP showed significantly higher delivery efficiency into APCs underlaying microfold (M) cells in Peyer's patches after oral administration in BALB/c mice and enhanced IL-12 production when αGalCer was conjugated to SlpB-LP. In conclusion, the present study demonstrates the therapeutic potential of SlpB-coated LP to deliver immunomodulatory components to the gut immune system.

摘要

通过与特定配体和交联试剂的缀合进行脂质体靶向是主动药物递送的一种有吸引力的策略。在这里,我们证明了短乳杆菌 JCM 1059 的表面层蛋白(Slp)B 作为一种针对派尔集合淋巴结中的抗原呈递细胞(APC)的特异性配体的潜力。与未涂层的脂质体(LPs)相比,SlpB 涂层的脂质体(SlpB-LPs)显示出更高的抵抗各种 pH 值和胆汁酸的能力。SlpB-LP 进入树突状细胞样分化的 THP-1 细胞的摄取率明显高于 LP。与 LP 相比,SlpB-LP 缀合的α-半乳糖神经酰胺(αGalCer)可促进 THP-1 细胞产生 IL-12(p40)和 TNF-α。此外,在 BALB/c 小鼠口服给药后,SlpB-LP 显示出在派尔集合淋巴结下的微褶皱(M)细胞下向 APC 输送的效率显著提高,并且当 αGalCer 缀合到 SlpB-LP 时,IL-12 的产生得到增强。总之,本研究证明了 SlpB 涂层 LP 将免疫调节成分递送到肠道免疫系统的治疗潜力。

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