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Nanoparticle Attachment to Erythrocyte Via the Glycophorin A Targeted ERY1 Ligand Enhances Binding without Impacting Cellular Function

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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.

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Abbreviations

BNP:

BSA-NPs

BSA:

Bovine serum albumin

ENP:

ERY1-BSA NPs

GPA:

Glycophorin A

GSH:

Glutathione

MDA:

Malondialdehyde

MIS:

Mismatch peptide

MNP:

MIS-BSA NPs

NP:

Nanoparticle

PDI:

Polydispersity index

PEG:

Polyethylene glycol

PLL:

Poly L-lysine

RBCs:

Red blood cells

TBARS:

Thiobarbituric acid reactive substances

TCA:

Trichloroacetic acid

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ACKNOWLEDGMENTS AND DISCLOSURES

We thank Marie Montelongo and the Oklahoma Center for Respiratory and Infectious Diseases Center (GM103648) for providing core-facility support and technical expertise. The content is solely the responsibility of the authors and does not necessarily represent the official views of the DTRA or ITP. A.R., J.L, C.P, J.R, and S.H. have patent interests in NP-mediated erythrocyte technology according to Oklahoma State University policies. K.S., N.F., R.H, P.C, and S.K. declare no competing financial interests.

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Authors and Affiliations

  1. Department of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, 74078, USA

    Kaustuv Sahoo, Jing Liu, Carey Pope & Ashish Ranjan

  2. School of Chemical Engineering, Oklahoma State University, Stillwater, Oklahoma, 74078, USA

    Rangika S. Hikkaduwa Koralege, Nicholas Flynn, Samyukta Koteeswaran, Peter Clark & Joshua D. Ramsey

  3. Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, Oklahoma, 74078, USA

    Steve Hartson

  4. Laboratory of Nanomedicine and Targeted Therapy, Center for Veterinary Health Sciences, Oklahoma State University, 169 McElroy Hall, Stillwater, Oklahoma, 74074, USA

    Ashish Ranjan

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  1. Kaustuv Sahoo
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Correspondence to Ashish Ranjan.

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Sahoo, K., Koralege, R.S.H., Flynn, N. et al. Nanoparticle Attachment to Erythrocyte Via the Glycophorin A Targeted ERY1 Ligand Enhances Binding without Impacting Cellular Function. Pharm Res 33, 1191–1203 (2016). https://doi.org/10.1007/s11095-016-1864-x

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  • DOI: https://doi.org/10.1007/s11095-016-1864-x

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