追踪具有“非自我”生物学身份的纳米粒子的体内命运。,ACS Nano

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追踪具有“非自我”生物学身份的纳米粒子的体内命运。
ACS Nano ( IF 15.8 ) Pub Date : 2020-08-07 , DOI: 10.1021/acsnano.0c05178
Hossein Mohammad-Beigi ₁ , Carsten Scavenius ₂ , Pia Bomholt Jensen ₁ , Kasper Kjaer-Sorensen ₂ , Claus Oxvig ₂ , Thomas Boesen ₁ , Jan J Enghild ₂ , Duncan S Sutherland ₁ , Yuya Hayashi ₂

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纳米粒子可以获取具有特定物种生物特征的生物分子电晕。但是，例如，当啮齿动物被用作生物分子启发的纳米药物的临床前研究的模型生物时，通常不考虑受体生物系统的“非自身”不相容性。使用斑马鱼胚胎作为纳米生物成像的新兴模型，在这里我们揭示了静脉注射70 nm SiO _2的体内命运由胎牛血清（FBS）制成的具有蛋白质电晕的纳米颗粒，代表一种非自身的生物学特性。在注射后数分钟内，在清除剂内皮细胞中观察到具有预先形成的FBS电晕的纳米颗粒惊人地快速隔离和溶酶体酸化。在数小时的过程中，这导致血管完整性的丧失和巨噬细胞的炎性活化。由于未经修饰的纳米颗粒或仅等量剂量的FBS蛋白无法诱导观察到的病理生理，这表明富含差异蛋白库的日冕如何确定体内纳米颗粒的命运。因此，我们的发现揭示了不相容的蛋白质电晕引发的不利结果，并表明在纳米药物开发过程中使用错配的物种组合存在潜在的陷阱。

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Tracing the In Vivo Fate of Nanoparticles with a "Non-Self" Biological Identity.

Nanoparticles can acquire a biomolecular corona with a species-specific biological identity. However, “non-self” incompatibility of recipient biological systems is often not considered, for example, when rodents are used as a model organism for preclinical studies of biomolecule-inspired nanomedicines. Using zebrafish embryos as an emerging model for nanobioimaging, here we unravel the in vivo fate of intravenously injected 70 nm SiO₂ nanoparticles with a protein corona preformed from fetal bovine serum (FBS), representing a non-self biological identity. Strikingly rapid sequestration and endolysosomal acidification of nanoparticles with the preformed FBS corona were observed in scavenger endothelial cells within minutes after injection. This led to loss of blood vessel integrity and to inflammatory activation of macrophages over the course of several hours. As unmodified nanoparticles or the equivalent dose of FBS proteins alone failed to induce the observed pathophysiology, this signifies how the corona enriched with a differential repertoire of proteins can determine the fate of the nanoparticles in vivo. Our findings thus reveal the adverse outcome triggered by incompatible protein coronas and indicate a potential pitfall in the use of mismatched species combinations during nanomedicine development.

更新日期：2020-08-25

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