Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, University Paris-Saclay, Châtenay-Malabry, France.
Faculty of Pharmacy, University of Paris-Sud, Chatenay Malabry, France.
Eur J Pharm Biopharm. 2018 Sep;130:48-58. doi: 10.1016/j.ejpb.2018.06.014. Epub 2018 Jun 20.
A faithful characterization of nanomedicine (NM) is needed for a better understanding of their in vivo outcomes. Size and surface charge are studied with well-established methods. However, other relevant parameters for the understanding of NM behavior in vivo remain largely inaccessible. For instance, the reactive surface of nanomedicines, which are often grafted with macromolecules to decrease their recognition by the immune system, is excluded from a systematic characterization. Yet, it is known that a subtle modification of NMs' surface characteristics (grafting density, molecular architecture and conformation of macromolecules) is at the root of major changes in the presence of biological components. In this work, a method that investigates the steric hindrance properties of the NMs' surface coverage based on its capacity to exclude or allow adsorption of well-defined proteins was developed based on capillary electrophoresis. A series of proteins with different molecular weights (MW) were used as molecular probes to screen their adsorption behavior on nanoparticles bearing different molecular architectures at their surface. This novel strategy evaluating to some degree a functionality of NMs can bring additional information about their shell property and might allow for a better perception of their behavior in the presence of biological components. The developed method could discriminate nanoparticles with a high surface coverage excluding high MW proteins from nanoparticles with a low surface coverage that allowed high MW proteins to adsorb on their surface. The method has the potential for further standardization and automation for a routine use. It can be applied in quality control of NMs and to investigate interactions between proteins and NM in different situations.
为了更好地理解纳米医学（NM）的体内结果，需要对其进行准确的描述。大小和表面电荷是通过成熟的方法进行研究的。然而，对于理解 NM 体内行为的其他相关参数，我们仍然知之甚少。例如，纳米药物的反应表面通常与大分子结合以降低其被免疫系统识别的能力，这一表面通常被排除在系统的特性描述之外。然而，人们已经知道，纳米药物表面特性（接枝密度、大分子的分子结构和构象）的微小改变是在存在生物成分的情况下导致其性质发生重大变化的根本原因。在这项工作中，基于毛细管电泳开发了一种方法，该方法基于纳米药物表面覆盖率排斥或允许吸附特定蛋白质的能力来研究其空间位阻特性。使用一系列具有不同分子量（MW）的蛋白质作为分子探针，筛选它们在表面具有不同分子结构的纳米颗粒上的吸附行为。这种评估纳米药物某种功能的新策略可以提供有关其外壳特性的附加信息，并可能更好地理解它们在存在生物成分时的行为。该方法具有进一步标准化和自动化的潜力，可用于常规应用。它可以应用于纳米药物的质量控制，并研究不同情况下蛋白质与 NM 之间的相互作用。
