International Journal of Nanomedicine (Nov 2020)
Distinct Proteins in Protein Corona of Nanoparticles Represent a Promising Venue for Endogenous Targeting – Part II: In vitro and in vivo Kinetics Study
Abstract
Aya Ahmed Sebak,1 Iman Emam Omar Gomaa,2 Aliaa Nabil ElMeshad,3 Mahmoud Hussien Farag,1 Ulrike Breitinger,4 Hans-Georg Breitinger,4 Mahmoud Hashem AbdelKader5,6 1Pharmaceutical Technology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo City, Egypt; 2Biochemistry Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt; 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 4Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo City, Egypt; 5National Institute of Laser Enhanced Sciences (NILES), Cairo University (CU), Giza, Egypt; 6European University in Egypt (EUE), New Administrative Capital, Cairo, EgyptCorrespondence: Aya Ahmed SebakFaculty of Pharmacy and Biotechnology, German University in Cairo (GUC), New Cairo City, EgyptTel +20 1205727787Email [email protected] Emam Omar GomaaBiochemistry Department Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, EgyptTel +20 1275146432Email [email protected]: 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.Methods: 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.Results: 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.Discussion: PC, if properly modulated by tuning NPs’ physicochemical properties, can serve as a potential venue for optimum utilization of NPs in cancer therapy.Keywords: Protein corona, endogenous targeting, melanoma, endocytosis, exocytosis, biodistribution, pharmacokinetics
