Key Laboratory of Drug- Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Mol Pharm. 2023 Jun 5;20(6):2978-2990. doi: 10.1021/acs.molpharmaceut.3c00021. Epub 2023 Apr 28.
Under physiological conditions, nanoparticles (NPs) inevitably interact with proteins, resulting in extensive protein adsorption and the formation of a protein corona. Recent studies have shown that the different surface properties of NPs lead to varying degrees of conformational changes of adsorbed proteins. However, the impact of corona protein conformation on the and profiles of NPs remain largely unexplored. Herein, d-α-tocopherol polyethylene glycol 1000 succinate-based NPs with natural human serum albumin (HSA) corona or thermally denatured HSA (HSA) corona were synthesized following a previously established method. We then conducted a systematic study of the protein conformation as well as adsorption behaviors. Additionally, the impact of protein corona conformation on the NPs profiles and were elucidated to gain insight into its biological behaviors as a targeted delivery system for renal tubule diseases. Overall, NPs modified by HSA corona showed improved serum stability, greater cell uptake efficiency, better renal tubular targetability, and therapeutic efficacy on acute kidney injury in rats than NPs modified by HSA corona. Hence, the conformation of protein adsorbed on the surface of NPs may impact the and profiles of NPs.
在生理条件下，纳米颗粒（NPs）不可避免地与蛋白质相互作用，导致广泛的蛋白质吸附和蛋白质冠的形成。最近的研究表明，NPs 的不同表面性质导致吸附蛋白质的构象发生不同程度的变化。然而，蛋白质冠构象对 NPs 的 和 分布的影响在很大程度上仍未得到探索。在此，我们采用先前建立的方法合成了基于 d-α-生育酚聚乙二醇 1000 琥珀酸酯的 NPs，其表面带有天然人血清白蛋白（HSA）冠或热变性 HSA（HSA）冠。然后，我们对蛋白质构象以及吸附行为进行了系统研究。此外，还阐明了蛋白质冠构象对 NPs 分布的影响，以深入了解其作为肾脏疾病靶向递药系统的生物学行为。总体而言，与 HSA 冠修饰的 NPs 相比，HSA 冠修饰的 NPs 具有更好的血清稳定性、更高的细胞摄取效率、更好的肾小管靶向性和对大鼠急性肾损伤的治疗效果。因此，吸附在 NPs 表面的蛋白质的构象可能会影响 NPs 的 和 分布。
