<br>蛋白质电晕的体内生物学命运：健康动物模型中软蛋白和硬蛋白电晕命运的 PET 比较研究,Small

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蛋白质电晕的体内生物学命运：健康动物模型中软蛋白和硬蛋白电晕命运的 PET 比较研究
Small ( IF 13.0 ) Pub Date : 2024-04-02 , DOI: 10.1002/smll.202309616
Angel Martinez Villacorta _{1,

2} , Angelika Mielcarek ₃ , María Gómez Martinez _{1,

4} , Helena Jorge ₁ , Agata Henschke ₃ , Emerson Coy ₃ , Vanessa Gomez-Vallejo ₁ , Jordi Llop ₁ , Sergio E Moya ₂

Affiliation

放射性标记和核成像技术用于研究给予健康小鼠后聚（乳酸-羟基乙酸共聚物）纳米颗粒（PLGA NPs）周围软蛋白和硬蛋白电晕的生物分布模式。¹³¹个 I 标记的 BSA 或 ¹³¹个 I 标记的血清的软蛋白和硬蛋白电晕在用聚乙烯亚胺（PEI）或牛血清白蛋白（BSA）功能化的 PLGA NP 上形成。通过伽马计数在体外评估硬电晕和软电晕的可交换性，将带有电晕的 PLGA NPs 暴露于未标记的 BSA、血清或模拟体液中。PEI PLGA NP 比 BSA PLGA NP 形成更大、更稳定的电晕。软电晕比硬电晕更容易交换。静脉内给药后，通过正电子发射断层扫描（PET）评估涂有预制 ¹⁸F 标记的 BSA 硬冠和软冠的 PEI PLGA NP 的体内命运。软电晕显示出类似于游离 ¹⁸F BSA 的生物分布，在血液和肾脏中具有高活性，而硬电晕遵循纳米颗粒的特征模式，在肺、肝和脾中积累。这些结果表明，软电晕和硬电晕在体内的命运不同，软电晕更容易与体内的蛋白质交换，而硬电晕主要保留在纳米颗粒表面。

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The In Vivo Biological Fate of Protein Corona: A Comparative PET Study of the Fate of Soft and Hard Protein Corona in Healthy Animal Models

Radiolabeling and nuclear imaging techniques are used to investigate the biodistribution patterns of the soft and hard protein corona around poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) after administration to healthy mice. Soft and hard protein coronas of ¹³¹I-labeled BSA or ¹³¹I-labeled serum are formed on PLGA NPs functionalized with either polyehtylenimine (PEI) or bovine serum albumin (BSA). The exchangeability of hard and soft corona is assessed in vitro by gamma counting exposing PLGA NPs with corona to non-labeled BSA, serum, or simulated body fluid. PEI PLGA NPs form larger and more stable coronas than BSA PLGA NPs. Soft coronas are more exchangeable than hard ones. The in vivo fate of PEI PLGA NPs coated with preformed ¹⁸F-labeled BSA hard and soft coronas is assessed by positron emission tomography (PET) following intravenous administration. While the soft corona shows a biodistribution similar to free ¹⁸F BSA with high activity in blood and kidney, the hard corona follows patterns characteristic of nanoparticles, accumulating in the lungs, liver, and spleen. These results show that in vivo fates of soft and hard corona are different, and that soft corona is more easily exchanged with proteins from the body, while hard corona is largely retained on the nanoparticle surface.

更新日期：2024-04-02

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