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磷脂酰丝氨酸在体外和体内将单壁碳纳米管靶向至专职吞噬细胞。

Phosphatidylserine targets single-walled carbon nanotubes to professional phagocytes in vitro and in vivo.

作者信息

Konduru Nagarjun V, Tyurina Yulia Y, Feng Weihong, Basova Liana V, Belikova Natalia A, Bayir Hülya, Clark Katherine, Rubin Marc, Stolz Donna, Vallhov Helen, Scheynius Annika, Witasp Erika, Fadeel Bengt, Kichambare Padmakar D, Star Alexander, Kisin Elena R, Murray Ashley R, Shvedova Anna A, Kagan Valerian E

机构信息

Department of Environmental and Occupational Health, Center for Free Radical and Antioxidant Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

出版信息

PLoS One. 2009;4(2):e4398. doi: 10.1371/journal.pone.0004398. Epub 2009 Feb 9.

DOI:10.1371/journal.pone.0004398
PMID:19198650
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2634966/
Abstract

Broad applications of single-walled carbon nanotubes (SWCNT) dictate the necessity to better understand their health effects. Poor recognition of non-functionalized SWCNT by phagocytes is prohibitive towards controlling their biological action. We report that SWCNT coating with a phospholipid "eat-me" signal, phosphatidylserine (PS), makes them recognizable in vitro by different phagocytic cells - murine RAW264.7 macrophages, primary monocyte-derived human macrophages, dendritic cells, and rat brain microglia. Macrophage uptake of PS-coated nanotubes was suppressed by the PS-binding protein, Annexin V, and endocytosis inhibitors, and changed the pattern of pro- and anti-inflammatory cytokine secretion. Loading of PS-coated SWCNT with pro-apoptotic cargo (cytochrome c) allowed for the targeted killing of RAW264.7 macrophages. In vivo aspiration of PS-coated SWCNT stimulated their uptake by lung alveolar macrophages in mice. Thus, PS-coating can be utilized for targeted delivery of SWCNT with specified cargoes into professional phagocytes, hence for therapeutic regulation of specific populations of immune-competent cells.

摘要

单壁碳纳米管（SWCNT）的广泛应用决定了有必要更好地了解其对健康的影响。吞噬细胞对未功能化的SWCNT识别能力差，这限制了对其生物学作用的控制。我们报告称，用磷脂“吃我”信号磷脂酰丝氨酸（PS）包被SWCNT，可使其在体外被不同的吞噬细胞识别，包括小鼠RAW264.7巨噬细胞、原代单核细胞衍生的人巨噬细胞、树突状细胞和大鼠脑小胶质细胞。PS结合蛋白膜联蛋白V和内吞抑制剂可抑制巨噬细胞对PS包被纳米管的摄取，并改变促炎和抗炎细胞因子的分泌模式。用促凋亡货物（细胞色素c）装载PS包被的SWCNT可实现对RAW264.7巨噬细胞的靶向杀伤。在体内吸入PS包被的SWCNT可刺激小鼠肺泡巨噬细胞对其摄取。因此，PS包被可用于将带有特定货物的SWCNT靶向递送至专业吞噬细胞，从而对免疫活性细胞的特定群体进行治疗性调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07b6/2634966/e4e9104b3671/pone.0004398.g008.jpg
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