Erythroliposomes: Integrated Hybrid Nanovesicles Composed of Erythrocyte Membranes and Artificial Lipid Membranes for Pore-Forming Toxin Clearance
Erythroliposomes: Integrated Hybrid Nanovesicles Composed of Erythrocyte Membranes and Artificial Lipid Membranes for Pore-Forming Toxin Clearance
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红脂质体：由红细胞膜和人工脂质膜组成的集成混合纳米囊泡，用于清除成孔毒素
DOI：
10.1021/acsnano.8b08964
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发表时间：
2019-04-01
期刊：
影响因子：
17.1
通讯作者：
Pang, Zhiqing
中科院分区：
文献类型：
--
作者：
He, Yuwei;Li, Ruixiang;Pang, Zhiqing
孔道形成毒素(PFTs)是最常见的细菌毒力蛋白，在细菌感染的发病机制中起着重要作用，因此PFTs是治疗细菌感染的一个有吸引力的靶点。受PFT的成孔过程和机理的启发，我们设计了一种用于PFT解毒的集成杂化纳米微囊--红脂体(简称RM-PL)，将天然红细胞膜与人造脂膜融合在一起。当脂质和红细胞膜整合成杂化纳米囊泡结构时，它们是互惠的。红细胞膜赋予Rm-pls解毒能力，而聚乙二醇化的脂膜稳定Rm-pls，大大提高红细胞膜的解毒能力。以α-溶血素(hlα)为模型，我们证明了rm-pls不仅在体外能显著降低hlα对红细胞的毒性，而且在体内也能有效地海绵hlα，使小鼠免受hlα所致的损伤。此外，Rm-pls的高解毒能力部分与红细胞膜上hlα受体蛋白的表达有关，hlα受体蛋白是一种含有去整合素和金属蛋白酶结构域的蛋白10。因此，作为一种整合天然和人工材料的成分，红脂体纳米平台激发了潜在的抗病毒治疗策略。
Pore-forming toxins (PFTs) are the most common bacterial virulence proteins and play a significant role in the pathogenesis of bacterial infections; thus, PFTs are an attractive therapeutic target in bacterial infections. Inspired by the pore-forming process and mechanism of PFTs, we designed an integrated hybrid nanovesicle-the erythroliposome (called the RM-PL)-for PFT detoxification by fusing natural red blood cell (RBC) membranes with artificial lipid membranes. The lipid and RBC membranes were mutually beneficial when integrated into a hybrid nanovesicle structure. The RBC membrane endowed RM-PLs with the capacity for detoxification, while the PEGylated lipid membrane stabilized the RM-PLs and greatly improved the detoxification capacity of the RBC membrane. With alpha-hemolysin (Hl alpha) as a model PFT, we demonstrated that RM-PLs could not only significantly reduce the toxicity of Hl alpha to erythrocytes in vitro but also effectively sponge Hl alpha in vivo and rescue mice from Hl alpha-induced damage. Moreover, the high detoxification capacity of RM-PLs was shown to be partly related to the expression of the Hl alpha receptor protein, a disintegrin and metalloproteinase domain-containing protein 10 on the RBC membrane. Consequently, as a component integrating natural and artificial materials, the erythroliposome nanoplatform inspires potential strategies for antivirulence therapy.