纳米颗粒的弹性通过调节在形成冠时的载脂蛋白 A-I 的吸附来影响全身循环寿命。
Nanoparticle elasticity affects systemic circulation lifetime by modulating adsorption of apolipoprotein A-I in corona formation.
机构信息
Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, 230026, Anhui, China.
CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, 230026, Anhui, China.
出版信息
Nat Commun. 2022 Jul 16;13(1):4137. doi: 10.1038/s41467-022-31882-4.
Nanoparticle elasticity is crucial in nanoparticles' physiological fate, but how this occurs is largely unknown. Using core-shell nanoparticles with a same PEGylated lipid bilayer shell yet cores differing in elasticity (45 kPa - 760 MPa) as models, we isolate the effects of nanoparticle elasticity from those of other physiochemical parameters and, using mouse models, observe a non-monotonic relationship of systemic circulation lifetime versus nanoparticle elasticity. Incubating our nanoparticles in mouse plasma provides protein coronas varying non-monotonically in composition depending on nanoparticle elasticity. Particularly, apolipoprotein A-I (ApoA1) is the only protein whose relative abundance in corona strongly correlates with our nanoparticles' blood clearance lifetime. Notably, similar results are observed when above nanoparticles' PEGylated lipid bilayer shell is changed to be non-PEGylated. This work unveils the mechanisms by which nanoparticle elasticity affects nanoparticles' physiological fate and suggests nanoparticle elasticity as a readily tunable parameter in future rational exploiting of protein corona.
纳米粒子的弹性在其生理命运中至关重要,但这是如何发生的在很大程度上是未知的。我们使用具有相同聚乙二醇化脂质双层壳但弹性不同的核壳纳米粒子(45 kPa-760 MPa)作为模型,将纳米粒子弹性的影响与其他物理化学参数的影响隔离开来,并使用小鼠模型观察到系统循环寿命与纳米粒子弹性之间的非单调关系。将我们的纳米粒子在小鼠血浆中孵育,会根据纳米粒子弹性产生组成非单调变化的蛋白质冠。特别是,载脂蛋白 A-I(ApoA1)是唯一一种其在冠中的相对丰度与我们的纳米粒子的血液清除半衰期强烈相关的蛋白质。值得注意的是,当上述纳米粒子的聚乙二醇化脂质双层壳被改变为非聚乙二醇化时,也观察到类似的结果。这项工作揭示了纳米粒子弹性如何影响纳米粒子的生理命运的机制,并表明纳米粒子弹性是未来合理利用蛋白质冠的一个可调节参数。