Kaustuv Sahoo1, Rangika S Hikkaduwa Koralege2, Nicholas Flynn2, Samyukta Koteeswaran2, Peter Clark2, Steve Hartson3, Jing Liu1, Joshua D Ramsey2, Carey Pope1, Ashish Ranjan4,5. 1. Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, 74078, USA. 2. School of Chemical Engineering, Oklahoma State University, Stillwater, Oklahoma, 74078, USA. 3. Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, Oklahoma, 74078, USA. 4. Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, 74078, USA. ashish.ranjan@okstate.edu. 5. Laboratory of Nanomedicine and Targeted Therapy, Center for Veterinary Health Sciences, Oklahoma State University, 169 McElroy Hall, Stillwater, Oklahoma, 74074, USA. ashish.ranjan@okstate.edu.
Abstract
PURPOSE: Nanoparticle (NP) attachment to biocompatible secondary carriers such as red blood cell (RBC) can prolong blood residence time of drug molecules and help create next-generation nanotherapeutics. However, little is known about the impact of RBC-targeted NPs on erythrocyte function. METHODS: The objectives of this study were to develop and characterize in vitro a novel poly-L-lysine (PLL) and polyethylene glycol (PEG) copolymer-based NP containing fluorescent-tagged bovine serum albumin (BSA), and conjugated with ERY1, a 12 amino acid peptide with high affinity for the RBC membrane protein glycophorin A (ENP). RESULTS: Confocal and flow cytometry data suggest that ENPs efficiently and irreversibly bind to RBC, with approximately 70% of erythrocytes bound after 24 h in a physiologic flow loop model compared to 10% binding of NPs without ERY1. Under these conditions, synthesized ENPs were not toxic to the RBCs. The rheological parameters at the applied shear. (0-15 Pa) were not influenced by ENP attachment to the RBCs. However, at high concentration, the strong affinity of ENPs to the glycophorin-A reduced the deformability of the RBC. CONCLUSIONS: ENPs can be efficiently attached to the RBCs without adversely affecting cellular function, and this may potentially enhance circulatory half-life of drug molecules.
PURPOSE: Nanoparticle (NP) attachment to biocompatible secondary carriers such as red blood cell (RBC) can prolong blood residence time of drug molecules and help create next-generation nanotherapeutics. However, little is known about the impact of RBC-targeted NPs on erythrocyte function. METHODS: The objectives of this study were to develop and characterize in vitro a novel poly-L-lysine (PLL) and polyethylene glycol (PEG) copolymer-based NP containing fluorescent-tagged bovineserum albumin (BSA), and conjugated with ERY1, a 12 amino acid peptide with high affinity for the RBC membrane protein glycophorin A (ENP). RESULTS: Confocal and flow cytometry data suggest that ENPs efficiently and irreversibly bind to RBC, with approximately 70% of erythrocytes bound after 24 h in a physiologic flow loop model compared to 10% binding of NPs without ERY1. Under these conditions, synthesized ENPs were not toxic to the RBCs. The rheological parameters at the applied shear. (0-15 Pa) were not influenced by ENP attachment to the RBCs. However, at high concentration, the strong affinity of ENPs to the glycophorin-A reduced the deformability of the RBC. CONCLUSIONS: ENPs can be efficiently attached to the RBCs without adversely affecting cellular function, and this may potentially enhance circulatory half-life of drug molecules.
Entities:
Keywords:
ERY1-ligand; glycophorin A targeting; nanoparticle; red blood cell; rheology
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