Lipopolysaccharide (LPS) is the primary bacterial toxin that is vital to the pathogenesis and progression of sepsis associated with extremely high morbidity and mortality worldwide. However, specific clearance of LPS from circulating blood is highly challenging because of the structural complexity and its variation between/within bacterial species. Herein, a robust strategy based on phage display screening and hemocompatible peptide bottlebrush polymer design for specific clearance of targeted LPS from circulating blood is proposed. Using LPS extracted from Escherichia coli as an example, a novel peptide (HWKAVNWLKPWT) with high affinity (K_D < 1.0 nм), specificity, and neutralization activity (95.9 ± 0.1%) against the targeted LPS is discovered via iterative affinity selection coupled with endotoxin detoxification screening. A hemocompatible bottlebrush polymer bearing the short peptide [poly(PEGMEA-co-PEP-1)] exhibits high LPS selectivity to reduce circulating LPS level from 2.63 ± 0.01 to 0.78 ± 0.05 EU mL⁻¹ in sepsis rabbits via extracorporeal hemoperfusion (LPS clearance ratio > 70%), reversing the LPS-induced leukocytopenia and multiple organ damages significantly. This work provides a universal paradigm for developing a highly selective hemoadsorbent library fully covering the LPS family, which is promising to create a new era of precision medicine in sepsis therapy.

中文翻译：

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基于肽瓶刷聚合物的血液中脂多糖的特异性清除用于脓毒症治疗

脂多糖（LPS）是主要的细菌毒素，对于脓毒症的发病机制和进展至关重要，脓毒症在全世界范围内具有极高的发病率和死亡率。然而，由于结构复杂性及其在细菌种类之间/内部的差异，从循环血液中特异性清除脂多糖非常具有挑战性。在此，提出了一种基于噬菌体展示筛选和血液相容性肽瓶刷聚合物设计的稳健策略，用于从循环血液中特异性清除目标 LPS。以从大肠杆菌中提取的 LPS为例，通过迭代亲和力选择与结合，发现了一种针对目标 LPS具有高亲和力 ( K _D < 1.0 nmм)、特异性和中和活性 (95.9 ± 0.1%) 的新型肽 (HWKAVNWLKPWT)。内毒素解毒筛查。带有短肽[聚(PEGMEA- co -PEP-1)]的血液相容性洗瓶刷聚合物表现出高LPS选择性，可通过体外血液灌流将脓毒症兔的循环LPS水平从2.63±0.01降低至0.78±0.05EUmL ⁻¹ （LPS清除率）比例> 70%），显着逆转LPS引起的白细胞减少和多器官损伤。这项工作为开发完全覆盖LPS家族的高选择性血液吸附剂库提供了通用范例，有望开创脓毒症治疗精准医学的新时代。