关键词: complement cascade dysopsonin innate pattern recognition molecules nanoparticle corona nanoparticle phagocytosis nanoparticle proteome nanoparticle stealthing polymers opsonin

Mesh : Animals Carrier Proteins Complement System Proteins / immunology metabolism Guidelines as Topic Humans Immunomodulation Macrophages / immunology metabolism Nanoparticles / chemistry Opsonin Proteins / administration & dosage chemistry immunology Phagocytes / immunology metabolism Protein Binding Proteome Theranostic Nanomedicine / methods

来  源:   DOI:10.3389/fimmu.2020.567365   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
Understanding the effects mediated by a set of nanoparticle (NP)-bound host biomolecules, often indicated with the umbrella term of NP corona, is essential in nanomedicine, nanopharmacology, and nanotoxicology. Among the NP-adsorbed proteome, some factors mediate cell binding, endocytosis, and clearing by macrophages and other phagocytes (opsonins), while some others display few affinities for the cell surface (dysopsonins). The functional mapping of opsonins and dysopsonins is instrumental to design long-circulating and nanotoxicologically safe next-generation nanotheranostics. In this review, we critically analyze functional data identifying specific proteins with opsonin or dysopsonin properties. Special attention is dedicated to the following: (1) the simplicity or complexity of the NP proteome and its modulation, (2) the role of specific host proteins in mediating the stealth properties of uncoated or polymer-coated NPs, and (3) the ability of the innate immune system, and, in particular, of the complement proteins, to mediate NP clearance by phagocytes. Emerging species-specific peculiarities, differentiating humans from preclinical animal models (the murine especially), are highlighted throughout this overview. The operative definition of opsonin and dysopsonin and the measurement schemes to assess their in vitro efficacy is critically re-examined. This provides a shared and unbiased approach useful for NP opsonin and dysopsonin systematic identification.
摘要:
了解由一组纳米颗粒(NP)结合的宿主生物分子介导的作用,通常用NP电晕的总称表示,在纳米医学中至关重要,纳米晶体学,和纳米毒理学。在NP吸附的蛋白质组中,一些因子介导细胞结合,内吞作用,并通过巨噬细胞和其他吞噬细胞(调理素)清除,而其他一些显示对细胞表面的亲和力很少(失调素)。调理素和调理素的功能图谱有助于设计长循环和纳米毒理学安全的下一代纳米热药。在这次审查中,我们严格地分析功能数据,确定具有调理素或失调素特性的特定蛋白质。特别注意以下方面:(1)NP蛋白质组及其调制的简单性或复杂性,(2)特定宿主蛋白在介导未包被或聚合物包被的NPs隐身特性中的作用,和(3)先天免疫系统的能力,and,特别是,补体蛋白,介导吞噬细胞清除NP。新兴的物种特异性特征,将人类与临床前动物模型(尤其是小鼠)区分开来,在整个概述中都突出显示。严格地重新检查了调理素和调理素异常的操作定义以及评估其体外功效的测量方案。这提供了一种共享且无偏见的方法,可用于NP调理素和调理素异常的系统鉴定。
公众号