title: Nanoparticle Attachment to Erythrocyte Via the Glycophorin A Targeted ERY1 Ligand Enhances Binding without Impacting Cellular Function.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, 74078, USA.
authors.forename: Kaustuv
authors.initials: K
authors.lastname: Sahoo
authors.affiliation: School of Chemical Engineering, Oklahoma State University, Stillwater, Oklahoma, 74078, USA.
authors.forename: Rangika S Hikkaduwa
authors.initials: RS
authors.lastname: Koralege
authors.affiliation: School of Chemical Engineering, Oklahoma State University, Stillwater, Oklahoma, 74078, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Flynn
authors.affiliation: School of Chemical Engineering, Oklahoma State University, Stillwater, Oklahoma, 74078, USA.
authors.forename: Samyukta
authors.initials: S
authors.lastname: Koteeswaran
authors.affiliation: School of Chemical Engineering, Oklahoma State University, Stillwater, Oklahoma, 74078, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Clark
authors.affiliation: Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, Oklahoma, 74078, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Hartson
authors.affiliation: Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, 74078, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Chemical Engineering, Oklahoma State University, Stillwater, Oklahoma, 74078, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Ramsey
authors.affiliation: Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, 74078, USA.
authors.forename: Carey
authors.initials: C
authors.lastname: Pope
authors.affiliation: Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, 74078, USA. ashish.ranjan@okstate.edu.|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.
authors.forename: Ashish
authors.initials: A
authors.lastname: Ranjan
mesh_terms: D000818:Animals; D002417:Cattle; D016503:Drug Delivery Systems; D004907:Erythrocyte Deformability; D004910:Erythrocyte Membrane / Q000378:metabolism*; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D006021:Glycophorins / Q000378:metabolism*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011107:Polylysine / Q000737:chemistry / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000008:administration & dosage
chemical_list: D006021:Glycophorins; D010455:Peptides; D011107:Polylysine; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols
keywords: ERY1-ligand; glycophorin A targeting; nanoparticle; red blood cell; rheology
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