研究人员研发出了一种人工合成的分子,它可让外来颗粒逃避免疫系统的检测。这种合成肽可被用来改善药物向肿瘤的输送并增进医学成像技术。目前的药物输送及成像策略受到了免疫系统快速识别并清除外来颗粒能力的阻碍。所谓的“自我”细胞通过被一种叫做CD47的膜蛋白标记而受到不被清除的保护。通过使用计算设计技术,Pia Rodriguez及其同事研发出了一种合成的基于人类CD47的肽。当研究人员将标记了该合成分子的纳米颗粒注射到小鼠体内时,该合成肽阻止了被称作吞噬细胞的白血球吞噬该纳米颗粒。该结果提示,这些合成肽是有效的逃避免疫系统的物质,它可能在多种应用中起到作用。(生物谷Bioon.com)
DOI: 10.1126/science.1229568
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Minimal "Self" Peptides That Inhibit Phagocytic Clearance and Enhance Delivery of Nanoparticles
P.L. Rodriguez; T. Harada; D.A. Christian; D.A. Pantano; R.K. Tsai; D.E. Discher
Foreign particles and cells are cleared from the body by phagocytes that must also recognize and avoid clearance of "self" cells. The membrane protein CD47 is reportedly a "marker of self" in mice that impedes phagocytosis of self by signaling through the phagocyte receptor CD172a. Minimal "Self" peptides were computationally designed from human CD47 and then synthesized and attached to virus-size particles for intravenous injection into mice that express a CD172a variant compatible with hCD47. Self peptides delay macrophage-mediated clearance of nanoparticles, which promotes persistent circulation that enhances dye and drug delivery to tumors. Self-peptide affinity for CD172a is near the optimum measured for human CD172a variants, and Self peptide also potently inhibits nanoparticle uptake mediated by the contractile cytoskeleton. The reductionist approach reveals the importance of human Self peptides and their utility in enhancing drug delivery and imaging.