Minimal "Self" peptides that inhibit phagocytic clearance and enhance delivery of nanoparticles.
Minimal "Self" peptides that inhibit phagocytic clearance and enhance delivery of nanoparticles.
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DOI：
10.1126/science.1229568
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发表时间：
2013-02-22
期刊：
影响因子：
--
通讯作者：
Discher DE
中科院分区：
文献类型：
--
作者：
Rodriguez PL;Harada T;Christian DA;Pantano DA;Tsai RK;Discher DE
吞噬细胞从体内清除外来颗粒和细胞，吞噬细胞还必须识别并避免清除“自身”细胞。据报道，膜蛋白 CD47 是小鼠的“自我标记”，它通过吞噬细胞受体 CD172a 发出信号来阻碍自我吞噬作用。通过计算设计人类 CD47 的最小“自身”肽，然后合成并附着到病毒大小的颗粒上，用于静脉注射到表达与 hCD47 兼容的 CD172a 变体的小鼠体内。自肽可延迟巨噬细胞介导的纳米粒子清除，从而促进持续循环，从而增强染料和药物向肿瘤的输送。自肽对 CD172a 的亲和力接近人类 CD172a 变体测量的最佳值，并且自肽还有效抑制由收缩细胞骨架介导的纳米颗粒摄取。还原论方法揭示了人类自身肽的重要性及其在增强药物输送和成像方面的效用。
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.
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影响因子：
14
作者：
Stachelek, Stanley J.;Finley, Matthew J.;Alferiev, Ivan S.;Wang, Fengxiang;Tsai, Richard K.;Eckells, Edward C.;Tomczyk, Nancy;Connolly, Jeanne M.;Discher, Dennis E.;Eckmann, David M.;Levy, Robert J.
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影响因子：
3.1
作者：
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通讯作者：
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