Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, UC San Diego School of Medicine, La Jolla, California (A.H., V.N.); and Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, La Jolla, California (V.N.).
Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, UC San Diego School of Medicine, La Jolla, California (A.H., V.N.); and Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego, La Jolla, California (V.N.)
J Pharmacol Exp Ther. 2024 May 21;389(3):289-300. doi: 10.1124/jpet.123.002095.
Invasive bacterial infections and sepsis are persistent global health concerns, complicated further by the escalating threat of antibiotic resistance. Over the past 40 years, collaborative endeavors to improve the diagnosis and critical care of septic patients have improved outcomes, yet grappling with the intricate immune dysfunction underlying the septic condition remains a formidable challenge. Anti-inflammatory interventions that exhibited promise in murine models failed to manifest consistent survival benefits in clinical studies through recent decades. Novel therapeutic approaches that target bacterial virulence factors, for example with monoclonal antibodies, aim to thwart pathogen-driven damage and restore an advantage to the immune system. A pioneering technology addressing this challenge is biomimetic nanoparticles-a therapeutic platform featuring nanoscale particles enveloped in natural cell membranes. Borne from the quest for a durable drug delivery system, the original red blood cell-coated nanoparticles showcased a broad capacity to absorb bacterial and environmental toxins from serum. Tailoring the membrane coating to immune cell sources imparts unique characteristics to the nanoparticles suitable for broader application in infectious disease. Their capacity to bind both inflammatory signals and virulence factors assembles the most promising sepsis therapies into a singular, pathogen-agnostic therapeutic. This review explores the ongoing work on immune cell-coated nanoparticle therapeutics for infection and sepsis. SIGNIFICANCE STATEMENT: Invasive bacterial infections and sepsis are a major global health problem made worse by expanding antibiotic resistance, meaning better treatment options are urgently needed. Biomimetic cell-membrane-coated nanoparticles are an innovative therapeutic platform that deploys a multifaceted mechanism to action to neutralize microbial virulence factors, capture endotoxins, and bind excessive host proinflammatory cytokines, seeking to reduce host tissue injury, aid in microbial clearance, and improve patient outcomes.
侵袭性细菌感染和败血症是持续存在的全球健康问题,而抗生素耐药性的不断升级使问题更加复杂。在过去的 40 年中,为改善败血症患者的诊断和重症监护而进行的合作努力改善了预后,但应对败血症患者潜在的复杂免疫功能障碍仍然是一个巨大的挑战。在过去的几十年中,在小鼠模型中表现出前景的抗炎干预措施并未在临床研究中显示出一致的生存获益。针对细菌毒力因子的新型治疗方法,例如使用单克隆抗体,旨在阻止病原体驱动的损伤并使免疫系统恢复优势。一种解决这一挑战的开创性技术是仿生纳米颗粒——一种具有纳米级颗粒的治疗平台,这些颗粒被天然细胞膜包裹。这种技术源于对持久药物输送系统的探索,最初的红细胞包被纳米颗粒展示出从血清中吸收细菌和环境毒素的广泛能力。对膜涂层进行免疫细胞来源的定制,赋予纳米颗粒独特的特性,使其更广泛地应用于传染病。它们结合炎症信号和毒力因子的能力将最有前途的败血症治疗方法组合成一种单一的、无病原体的治疗方法。本综述探讨了用于感染和败血症的免疫细胞包被纳米颗粒治疗的最新进展。重要性声明:侵袭性细菌感染和败血症是一个主要的全球健康问题,抗生素耐药性的不断扩大使问题更加严重,这意味着迫切需要更好的治疗选择。仿生细胞膜包被纳米颗粒是一种创新的治疗平台,它采用多方面的作用机制来中和微生物毒力因子、捕获内毒素,并结合过多的宿主促炎细胞因子,旨在减少宿主组织损伤、帮助清除微生物并改善患者预后。