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人内源性生物分子冠对聚乙二醇化脂质体的影响:概念验证性临床研究。

The Human In Vivo Biomolecule Corona onto PEGylated Liposomes: A Proof-of-Concept Clinical Study.

机构信息

Nanomedicine Lab, Faculty of Biology, Medicine and Health, The University of Manchester, AV Hill Building, Manchester, M13 9PT, UK.

Manchester Cancer Research Centre Biobank, The Christie NHS Foundation Trust, CRUK Manchester Institute, Manchester, M20 4BX, UK.

出版信息

Adv Mater. 2019 Jan;31(4):e1803335. doi: 10.1002/adma.201803335. Epub 2018 Nov 28.

DOI:10.1002/adma.201803335
PMID:30488990
Abstract

The self-assembled layered adsorption of proteins onto nanoparticle (NP) surfaces, once in contact with biological fluids, is termed the "protein corona" and it is gradually seen as a determinant factor for the overall biological behavior of NPs. Here, the previously unreported in vivo protein corona formed in human systemic circulation is described. The human-derived protein corona formed onto PEGylated doxorubicin-encapsulated liposomes (Caelyx) is thoroughly characterized following the recovery of liposomes from the blood circulation of ovarian carcinoma patients. In agreement with previous investigations in mice, the in vivo corona is found to be molecularly richer in comparison to its counterpart ex vivo corona. The intravenously infused liposomes are able to scavenge the blood pool and surface-capture low-molecular-weight, low-abundance plasma proteins that cannot be detected by conventional plasma proteomic analysis. This study describes the previously elusive or postulated formation of protein corona around nanoparticles in vivo in humans and illustrates that it can potentially be used as a novel tool to analyze the blood circulation proteome.

摘要

蛋白质在纳米颗粒(NP)表面的自组装层状吸附,一旦与生物流体接触,就被称为“蛋白质冠”,它逐渐被视为 NP 整体生物行为的决定因素。在这里,描述了以前未在体内报道过的人系统循环中形成的蛋白质冠。从卵巢癌患者的血液循环中回收载有阿霉素的 PEG 化脂质体(Caelyx)后,对其形成的人源性蛋白质冠进行了彻底的表征。与之前在小鼠中的研究一致,与体外冠相比,体内冠在分子上更为丰富。静脉内输注的脂质体能够清除血池并表面捕获低分子量、低丰度的血浆蛋白,这些蛋白无法通过常规的血浆蛋白质组学分析检测到。本研究描述了以前在体内难以捉摸或推测的纳米颗粒周围蛋白质冠的形成,并说明了它可能被用作分析血液循环蛋白质组的新工具。

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