Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster, Corrensstr, 48149 Muenster, Germany.
Institute of Food Chemistry, University of Muenster, Corrensstr, 48149 Muenster, Germany.
Eur J Pharm Biopharm. 2021 Jun;163:212-222. doi: 10.1016/j.ejpb.2021.04.006. Epub 2021 Apr 20.
Poly(DL-lactic-co-glycolic acid) and poly(DL-lactic acid) are widely used for the preparation of nanoparticles due to favorable characteristics for medical use like biodegradability and controllable degradation behavior. The contact with different media like human plasma or serum leads to the formation of a protein corona that determines the NP's in vivo processing. In this study, the impact of surface end group identity, matrix polymer hydrophobicity, molecular weight, and incubation medium on the protein corona composition was evaluated. Corona proteins were quantified using Bradford assay, separated by SDS-PAGE, and identified via LC-MS/MS. The acquired data revealed that surface end group identity had the most profound effect on corona composition in both quantitative and qualitative terms. Regarding matrix polymer hydrophobicity, adsorption profiles on NP systems with similar physicochemical characteristics resembled each other. The molecular weight of the matrix polymers proved to impact quantity, but not quality of corona bound proteins. The corona of plasma incubated NP showed adsorption of incubation medium-specific proteins but resembled those of serum incubated NP in terms of protein function, average mass and isoelectric point. Overall, the NP physicochemical properties proved to be easily adjustable determining factors of protein corona formation in physiological environments.
聚（DL-丙交酯-共-乙交酯）和聚（DL-丙交酯）由于具有可生物降解性和可控制的降解行为等有利于医疗用途的特性，因此被广泛用于制备纳米粒子。与人体血浆或血清等不同介质的接触会导致形成蛋白质冠，从而决定 NP 的体内处理。在这项研究中，评估了表面端基的身份、基质聚合物疏水性、分子量和孵育介质对蛋白质冠组成的影响。使用 Bradford 测定法定量测定了冠层蛋白，通过 SDS-PAGE 进行分离，并通过 LC-MS/MS 进行鉴定。获得的数据表明，表面端基的身份在定量和定性方面对冠层组成的影响最为深远。关于基质聚合物疏水性，具有相似物理化学特性的 NP 系统的吸附曲线彼此相似。基质聚合物的分子量证明会影响结合蛋白的数量，但不会影响其质量。与孵育血清的 NP 相比，在等离子体孵育的 NP 的蛋白质冠层中吸附了特定于孵育介质的蛋白质，但在蛋白质功能、平均质量和等电点方面与孵育血清的 NP 相似。总的来说，NP 的物理化学性质被证明是在生理环境中形成蛋白质冠的易于调节的决定因素。
