College of Pharmaceutical and Bioengineering, Shenyang University of Chemical Technology, Shenyang 110142, China.
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
ACS Appl Mater Interfaces. 2023 Jul 12;15(27):32251-32261. doi: 10.1021/acsami.3c05341. Epub 2023 Jun 28.
Blood infection can release toxic bacterial lipopolysaccharides (LPSs) into bloodstream, trigger a series of inflammatory reactions, and eventually lead to multiple organ dysfunction, irreversible shock, and even death, which seriously threatens human life and health. Herein, a functional block copolymer with excellent hemocompatibility is proposed to enable broad-spectrum clearance of LPSs from whole blood blindly before pathogen identification, facilitating timely rescue from sepsis. A dipeptide ligand of histidine-histidine (HH) was designed as the LPS binding unit, and poly[(trimethylamine -oxide)--(histidine-histidine)], a functional block copolymer combining the LPS ligand of HH and a zwitterionic antifouling unit of trimethylamine -oxide (TMAO), was then designed by reversible addition-fragmentation chain transfer (RAFT) polymerization. The functional polymer achieved effective clearance of LPSs from solutions and whole blood in a broad-spectrum manner and had good antifouling and anti-interference properties and hemocompatibility. The proposed functional dihistidine polymer provides a novel strategy for achieving broad-spectrum clearance of LPSs, with potential applications in clinical blood purification.
血液感染会将有毒的细菌脂多糖（LPSs）释放到血液中，引发一系列炎症反应，最终导致多器官功能障碍、不可逆性休克，甚至死亡，严重威胁着人类的生命和健康。在此，我们提出了一种具有良好血液相容性的功能性嵌段共聚物，它可以在确定病原体之前从全血中盲目清除广谱 LPSs，有助于及时从败血症中抢救。我们将组氨酸-组氨酸（HH）二肽配体设计为 LPS 结合单元，然后通过可逆加成-断裂链转移（RAFT）聚合设计了一种结合 HH 配体和两性离子抗污单元三甲基氧化胺（TMAO）的功能性嵌段共聚物聚[（三甲基氧化胺）-（组氨酸-组氨酸）]。该功能性聚合物能够在广谱范围内有效清除溶液和全血中的 LPSs，具有良好的抗污、抗干扰和血液相容性。所提出的功能性二组氨酸聚合物为实现广谱 LPSs 的清除提供了一种新策略，具有在临床血液净化中应用的潜力。
