Protein corona can alter the physiochemical properties of targeting nanoparticles (NPs), as well as their physiological responses and targeting functionality. Herein, we synthesized 20 types of NPs with diverse surface chemistry in order to study the impacts of protein corona on targeting functionality of NPs functionalized with cyclic RGD peptides and their relationships to the polyethylene glycol (PEG) length and grafting density of targeting ligands. After protein adsorption, cyclic RGD on the surface of NP was still able to bind its receptors with increased targeted cellular uptake, even at a relatively low density. However, the cellular uptake was reduced from 26 to 76% when compared with protein nonbound NPs, which was caused by the shielding effect of the outer layer adsorbed proteins. NPs functionalized with short PEG molecules and moderate cyclic RGD density performed a better targeting efficiency. Due to PEG conjugation, the protein corona was demonstrated to be beneficial for passive targeting by decreasing macrophage cellular uptake. These relationships between surface chemistry and targeting functionality will provide guidelines for the design of targeting nanoformulations in nanomedicine.

中文翻译：

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蛋白电晕对环状RGD肽功能化聚乙二醇化纳米粒子主动和被动靶向的影响。

蛋白电晕可以改变靶向纳米颗粒（NPs）的生理化学特性，以及它们的生理反应和靶向功能。在本文中，我们合成了20种具有不同表面化学性质的NP，以研究蛋白质电晕对用环状RGD肽官能化的NP的靶向功能的影响及其与聚乙二醇（PEG）长度和靶向配体的接枝密度的关系。蛋白质吸附后，即使在相对较低的密度下，NP表面的环状RGD仍然能够以增加的靶向细胞摄取结合其受体。但是，与蛋白质未结合的NP相比，细胞摄取从26％降低到76％，这是由于外层吸附蛋白质的屏蔽作用所致。用短PEG分子和适度的环状RGD密度官能化的NP具有更好的靶向效率。由于PEG的结合，蛋白晕被证明可通过减少巨噬细胞的细胞摄取而有利于被动靶向。表面化学和靶向功能之间的这些关系将为纳米药物中靶向纳米制剂的设计提供指导。