School of Pharmacy, Newcastle University, Newcastle upon Tyne NE1 7RU, UK; Translational and Clinical Research Institute, Faculty of Health and Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Colorado Center for Nanomedicine and Nanosafety, University of Colorado Anschutz Medical Center, Aurora, CO, USA.
School of Pharmacy, Newcastle University, Newcastle upon Tyne NE1 7RU, UK; Translational and Clinical Research Institute, Faculty of Health and Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
J Control Release. 2022 Nov;351:432-443. doi: 10.1016/j.jconrel.2022.09.039. Epub 2022 Sep 27.
The contribution of the complement system to non-specific host defence and maintenance of homeostasis is well appreciated. Many particulate systems trigger complement activation but the underlying mechanisms are still poorly understood. Activation of the complement cascade could lead to particle opsonisation by the cleavage products of the third complement protein and might promote inflammatory reactions. Antibody binding in a controlled manner and/or sensing of particles by the complement pattern-recognition molecules such as C1q and mannose-binding lectin can trigger complement activation. Particle curvature and spacing arrangement/periodicity of surface functional groups/ligands are two important parameters that modulate complement responses through multivalent engagement with and conformational regulation of surface-bound antibodies and complement pattern-recognition molecules. Thus, a better fundamental understanding of nanometer- and angstrom-scale parameters that modulate particle interaction with antibodies and complement proteins could portend new possibilities for engineering of particulate drug carriers and biomedical platforms with tuneable complement responses and is discussed here.
补体系统对非特异性宿主防御和维持体内平衡的贡献是众所周知的。许多颗粒系统会触发补体激活，但潜在的机制仍知之甚少。补体级联的激活可能导致颗粒被第三补体蛋白的裂解产物调理，并可能促进炎症反应。抗体以受控的方式结合，或者补体模式识别分子（如 C1q 和甘露糖结合凝集素）感知颗粒，可以触发补体激活。颗粒曲率和表面功能基团/配体的间隔排列/周期性是两个重要参数，它们通过与表面结合的抗体和补体模式识别分子的多价结合和构象调节来调节补体反应。因此，更好地理解纳米级和埃级参数，这些参数调节颗粒与抗体和补体蛋白的相互作用，可能为工程具有可调补体反应的颗粒药物载体和生物医学平台带来新的可能性，本文对此进行了讨论。
