Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
NMPA Key Laboratory for Monitoring and Evaluation of Cosmetics, Shanghai Institute for Food and Drug Control, Shanghai 201203, China.
ACS Nano. 2021 Mar 23;15(3):4173-4185. doi: 10.1021/acsnano.0c04800. Epub 2021 Feb 19.
Antivirulence therapy by cell membrane coated nanoparticles has shown promise against bacterial infections. However, current approaches remain unsatisfactory when facing () infections, since the secretes multiple bacterial toxins including endotoxins and exotoxins that are challenging to eliminate simultaneously. What is worse, the absorptive scavengers normally rely on random contact of the diffuse toxins, which is not efficient. For the current cell membrane coated platform, the single type of cell membrane cannot fully meet the detoxing requirement facing multiple toxins. To address these problems, a polymyxin B (PMB)-modified, red blood cell (RBC)-mimetic hybrid liposome (P-RL) was developed. The P-RL was fabricated succinctly through fusion of PMB-modified lipids and the RBC membranes. By the strong interaction between PMB and the membrane, P-RL could attach and anchor to the ; attributed to the fused RBC membrane and modified PMB, the P-RL could then efficiently neutralize both endotoxins and exotoxins from the toxin fountainhead. and results demonstrated the P-RL had a significant anchoring effect to . Moreover, compared with the existing RBC vesicles or PMB-modified liposomes, P-RL exhibited a superior therapeutic effect against RBC hemolysis, macrophage activation, and a mixed-toxin infection in mice. Potently, P-RL could inhibit O157:H7-induced skin damage, intestinal infection, and mouse death. Overall, the P-RL could potentially improve the detoxing efficiency and markedly expand the detoxification spectrum of current antivirulence systems, which provides different insights into drug-resistant treatment.
细胞膜包覆纳米粒子的抗毒疗法已显示出对抗细菌感染的潜力。然而，当前的方法在面对 （）感染时仍然不尽如人意，因为 分泌多种细菌毒素，包括内毒素和外毒素，同时消除这些毒素具有挑战性。更糟糕的是，吸收性清除剂通常依赖于弥散毒素的随机接触，这效率不高。对于当前的细胞膜包覆平台，单一类型的细胞膜不能完全满足面对多种毒素的解毒要求。为了解决这些问题，开发了一种多粘菌素 B（PMB）修饰的、红细胞（RBC）模拟的混合脂质体（P-RL）。通过 PMB 修饰的脂质与 RBC 膜的融合，简洁地制备了 P-RL。由于 PMB 与 膜之间的强相互作用，P-RL 可以附着并锚定在 上；由于融合的 RBC 膜和修饰的 PMB，P-RL 可以从毒素源头有效地中和内毒素和外毒素。 和 结果表明，P-RL 对 具有显著的锚定作用。此外，与现有的 RBC 囊泡或 PMB 修饰的脂质体相比，P-RL 对 RBC 溶血、巨噬细胞激活和混合毒素感染的小鼠表现出更好的治疗效果。强有力的是，P-RL 可以抑制 O157:H7 诱导的皮肤损伤、肠道感染和小鼠死亡。总的来说，P-RL 有可能提高解毒效率，并显著扩大当前抗毒系统的解毒谱，为耐药 治疗提供了不同的思路。
