Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification.
Controlled Delivery of an Anti-Inflammatory Toxin to Macrophages by Mutagenesis and Nanoparticle Modification.
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DOI：
10.3390/nano12132161
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发表时间：
2022-06-23
期刊：
影响因子：
5.3
通讯作者：
Niidome, Takuro
中科院分区：
文献类型：
--
作者：
Harada, Ayaka;Tsutsuki, Hiroyasu;Zhang, Tianli;Yahiro, Kinnosuke;Sawa, Tomohiro;Niidome, Takuro
药物递送系统(DDSS)的进展使药物能够特定地递送到靶细胞。某些肠出血性大肠杆菌菌株产生的枯草杆菌细胞毒素(SubAB)可诱导内质网应激，抑制巨噬细胞产生一氧化氮。我们先前报道，用聚(D，L-丙交酯-乙醇酸共聚)纳米粒(SubAB-PLGA NPs)修饰SubAB可以增加细胞内对SubAB的摄取，并对巨噬细胞具有抗炎作用。然而，由于SubAB对其他类型细胞的影响是不可忽视的，因此无法实现SubAB对巨噬细胞的特异性递送。因此，为了抑制非特异性的SubAB结合，我们使用了低结合突变体SubABS35A(S35A)，其中B亚基的第35个丝氨酸突变为丙氨酸。在巨噬细胞系中，S35A修饰的PLGA纳米粒(S35A-PLGA纳米粒)诱导内质网应激，并具有与WT-PLGA纳米粒相似的抗炎作用。然而，在上皮细胞系中，S35A-PLGA纳米颗粒比WT-PLGA纳米颗粒诱导的内质网应激更低。这些结果表明，通过PLGA纳米粒的修饰，S35A可以选择性地输送到巨噬细胞而不是上皮细胞，并发挥抗炎作用。我们的发现为将蛋白质输送到巨噬细胞提供了一种有用的技术，并鼓励DDSS在治疗炎症性疾病方面的医学应用。
Advances in drug delivery systems (DDSs) have enabled the specific delivery of drugs to target cells. Subtilase cytotoxin (SubAB) produced by certain enterohemorrhagic Escherichia coli strains induces endoplasmic reticulum (ER) stress and suppresses nitric oxide generation in macrophages. We previously reported that modification of SubAB with poly(D,L-lactide-co-glycolic) acid (PLGA) nanoparticles (SubAB-PLGA NPs) increased intracellular uptake of SubAB and had an anti-inflammatory effect on macrophages. However, specific delivery of SubAB to macrophages could not be achieved because its effects on other cell types were not negligible. Therefore, to suppress non-specific SubAB binding, we used low-binding mutant SubABS35A (S35A) in which the 35th serine of the B subunit was mutated to alanine. In a macrophage cell line, PLGA NPs modified with S35A (S35A-PLGA NPs) induced ER stress and had anti-inflammatory effects similar to WT-PLGA NPs. However, in an epithelial cell line, S35A-PLGA NPs induced lower ER stress than WT-PLGA NPs. These results suggest that S35A is selectively delivered to macrophages rather than epithelial cells by modification with PLGA NPs and exerts anti-inflammatory effects. Our findings provide a useful technique for protein delivery to macrophages and encourage medical applications of DDSs for the treatment of inflammatory diseases.
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DOI：
10.1016/j.bbamcr.2013.03.007
发表时间：
2013-11
影响因子：
5.1
作者：
Gidalevitz, Tali;Stevens, Fred;Argon, Yair
通讯作者：
Argon, Yair
DOI：
10.1007/s10856-021-06623-6
发表时间：
2021-12-04
期刊：
Journal of materials science. Materials in medicine
影响因子：
--
作者：
Barani M;Hajinezhad MR;Sargazi S;Rahdar A;Shahraki S;Lohrasbi-Nejad A;Baino F
通讯作者：
Baino F
影响因子：
3.8
作者：
Chen, Xi;Zhong, Jianxiang;Yang, Peixin
通讯作者：
Yang, Peixin
影响因子：
14
作者：
Cruz, Luis J.;van Dijk, Thamar;Eich, Christina
通讯作者：
Eich, Christina
影响因子：
64.8
作者：
Byres, Emma;Paton, Adrienne W.;Paton, James C.;Lofling, Jonas C.;Smith, David F.;Wilce, Matthew C. J.;Talbot, Ursula M.;Chong, Damien C.;Yu, Hai;Huang, Shengshu;Chen, Xi;Varki, Nissi M.;Varki, Ajit;Rossjohn, Jamie;Beddoe, Travis
通讯作者：
Beddoe, Travis