Pharmaceutical Technology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo City, Egypt.
Biochemistry Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt.
Int J Nanomedicine. 2020 Nov 30;15:9539-9556. doi: 10.2147/IJN.S273721. eCollection 2020.
Nanoparticles (NPs), upon introduction to the biological systems, become wrapped by serum and cellular proteins constituting the protein corona (PC). This PC contributes largely to the NPs' interaction with the biological systems and their subsequent functions. On the one hand, PC can decrease the efficiency of targeting by directing the NPs to the reticuloendothelial system (RES) or by masking the active targeting moieties and decreasing their ability to bind to their target receptors. On the other hand, some components of PC have offered hopes for achieving endogenous targeting.
In this study, we aimed at the investigation of the role of the PC in determining the behavior of cRGDyk peptide-unconjugated and -conjugated NPs (uNPs and cNPs) exhibiting different physicochemical properties and their interaction with melanoma on in vitro and in vivo levels. Mathematical modeling has been utilized to understand the kinetics of the interaction of NPs with the tumor cells and different organs, respectively.
Endocytosis and exocytosis were reported to occur simultaneously for the utilized NPs. The balance was largely dependent on the NPs' physicochemical properties and the role of the PC. In addition, distinct proteins present in the PC (illustrated in the results of the PC analysis in part I) have also determined the patterns of the NPs' distribution in different organs and tissues of the vascular system, the RES system and the target tumot tissue. Vitronectin (VN) was found to mediate higher accumulation in integrin receptor-expressing melanoma cells, while complement 3 protein (C3) and clusterin (CLU), as an opsonin and dysopsonin, respectively, regulated the balance between the RES uptake and blood circulation.
PC, if properly modulated by tuning NPs' physicochemical properties, can serve as a potential venue for optimum utilization of NPs in cancer therapy.
纳米粒子（NPs）进入生物系统后，会被血清和细胞蛋白包裹，形成蛋白质冠（PC）。PC 极大地影响了 NPs 与生物系统的相互作用及其后续功能。一方面，PC 可以通过将 NPs 导向网状内皮系统（RES）或掩盖主动靶向部分，降低其与靶受体结合的能力，从而降低靶向效率。另一方面，PC 的一些成分为实现内源性靶向提供了希望。
在这项研究中，我们旨在研究 PC 在决定 cRGDyk 肽未缀合和缀合 NPs（uNPs 和 cNPs）行为中的作用，这些 NPs 表现出不同的物理化学性质，并在体外和体内水平上研究其与黑色素瘤的相互作用。数学模型被用于理解 NPs 与肿瘤细胞和不同器官相互作用的动力学。
据报道，内吞作用和外排作用同时发生在所用的 NPs 上。这种平衡在很大程度上取决于 NPs 的物理化学性质和 PC 的作用。此外，PC 中存在的不同蛋白质（在第一部分的 PC 分析结果中说明）也决定了 NPs 在血管系统、RES 系统和靶肿瘤组织的不同器官和组织中的分布模式。纤连蛋白（VN）被发现介导整合素受体表达的黑色素瘤细胞中更高的积累，而补体 3 蛋白（C3）和簇蛋白（CLU）分别作为调理素和调理素，调节 RES 摄取和血液循环之间的平衡。
如果通过调整 NPs 的物理化学性质来适当调节 PC，可以为在癌症治疗中最佳利用 NPs 提供潜在的途径。
