Cell Membrane Modification for Rapid Display of Bi-Functional Peptides: A Novel Approach to Reduce Complement Activation

Goga, Ledia; Perez-Abadia, Gustavo; Pushpakumar, Sathnur B; Cramer, Daniel; Yan, Jun; Todnem, Nathan; Anderson, Gary; Soni, Chirag; Barker, John; Maldonado, Claudio

Cell Membrane Modification for Rapid Display of Bi-Functional Peptides: A Novel Approach to Reduce Complement Activation

Ledia Goga¹, Gustavo Perez-Abadia¹, Sathnur B Pushpakumar¹, Daniel Cramer², Jun Yan², Nathan Todnem¹, Gary Anderson¹, Chirag Soni¹, John Barker³, Claudio Maldonado^{1, *}

¹ Department of Physiology and Biophysics

² Department of Tumor Immunobiology

³ Department of Surgery, University of Louisville, Louisville, KY 40292, USA

Article Information

Identifiers and Pagination:

Year: 2010
Volume: 4
First Page: 157
Last Page: 165
Publisher ID: TOCMJ-4-157
DOI: 10.2174/1874192401004010157

Article History:

Received Date: 18/5/2010
Revision Received Date: 28/5/2010
Acceptance Date: 31/5/2010
Electronic publication date: 20/7/2010
Collection year: 2010

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© Goga et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

^* Address correspondence to this author at the Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky 40292 USA; Tel: 502-852-1078; Fax: 502-852-1256; E-mail: cjmald01@louisville.edu, cjmald01@gmail.com

Ischemia and reperfusion of organs is an unavoidable consequence of transplantation. Inflammatory events associated with reperfusion injury are in part attributed to excessive complement activation. Systemic administration of complement inhibitors reduces reperfusion injury but leaves patients vulnerable to infection. Here, we report a novel therapeutic strategy that decorates cells with an anti-complement peptide. An analog of the C3 convertase inhibitor Compstatin (C) was synthesized with a hexahistidine (His₆) tag to create C-His₆. To decorate cell membranes with C-His₆, fusogenic lipid vesicles (FLVs) were used to incorporate lipids with nickel (Ni²⁺) tethers into cell membranes, and these could then couple with C-His₆. Ni²⁺ tether levels to display C-His₆ were modulated by changing FLV formulation, FLV incubation time and FLV levels. SKOV-3 cells decorated with C-His₆ effectively reduced complement deposition in a classical complement activation assay. We conclude that our therapeutic approach appears promising for local ex vivo treatment of transplanted organs to reduce complement-mediated reperfusion injury.

Keywords: Complement, Complement inhibitors, Compstatin, Drug delivery, Liposomes, Ischemia, Reperfusion, Cell membrane..

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RESEARCH ARTICLE

Cell Membrane Modification for Rapid Display of Bi-Functional Peptides: A Novel Approach to Reduce Complement Activation

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Abstract

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About the Editor

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The Open Cardiovascular Medicine Journal

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