Max Planck Tandem Group in Nanobioengineering, Institute of Chemistry, Faculty of Natural and Exact Sciences, University of Antioquia, Complejo Ruta N, Calle 67 No 52-20, Medellin, 050010, Colombia.
Max Planck Institute for Polymer Research, 55128, Mainz, Germany.
Macromol Biosci. 2024 Feb;24(2):e2300197. doi: 10.1002/mabi.202300197. Epub 2023 Sep 10.
Encapsulating drugs into functionalized nanoparticles (NPs) is an alternative to reach the specific therapeutic target with lower doses. However, when the NPs are in contact with physiological media, proteins adsorb on their surfaces, forming a protein corona (PC) biomolecular layer, acquiring a distinct biological identity that alters their interactions with cells. Itraconazole (ITZ), an antifungal agent, is encapsulated into PEGylated and/or functionalized NPs with high specificity for macrophages. It is evaluated how the PC impacts their cell uptake and antifungal effect. The minimum inhibitory concentration and colony-forming unit assays demonstrate that encapsulated ITZ into poly(ethylene glycol) (PEG) NPs improves the antifungal effect compared with NPs lacking PEGylation. The improvement can be related to the synergistic effect of the encapsulated ITZ and NPs composition and the reduction of PC formation in PEG NPs. Functionalized NPs with anti-F4/80 and anti-MARCO antibodies, or mannose without PEG and treated with PC, show an improved uptake but, in the presence of PEG, significantly reduce the endocytosis, dominating the stealth effect from PEG. Therefore, the PC plays a crucial role in the nanosystem uptake and antifungal effects, which suggests the need for in vivo model studies to evaluate the effect of PC in the specificity and biodistribution.
将药物封装到功能化的纳米颗粒（NPs）中是一种用较低剂量达到特定治疗靶点的替代方法。然而，当 NPs 与生理介质接触时，蛋白质会吸附在它们的表面上，形成一个蛋白质冠（PC）生物分子层，获得独特的生物学身份，从而改变它们与细胞的相互作用。伊曲康唑（ITZ）是一种抗真菌药物，被封装到具有高特异性的巨噬细胞的聚乙二醇化和/或功能化 NPs 中。评估了 PC 如何影响它们的细胞摄取和抗真菌作用。最低抑菌浓度和集落形成单位测定表明，与缺乏聚乙二醇化的 NPs 相比，将 ITZ 封装到聚乙二醇（PEG） NPs 中可提高抗真菌效果。这种改善可能与封装 ITZ 和 NPs 组成的协同作用以及 PEG NPs 中 PC 形成的减少有关。具有抗 F4/80 和 MARCO 抗体的功能化 NPs 或没有 PEG 的甘露糖，以及用 PC 处理的功能化 NPs，表现出改善的摄取，但在 PEG 存在下，显著降低了内吞作用，主导了来自 PEG 的隐身效应。因此，PC 在纳米系统摄取和抗真菌作用中起着至关重要的作用，这表明需要进行体内模型研究来评估 PC 在特异性和生物分布中的作用。
