Title

Liposomes Impede Exotoxins Cytolytic Effects

Document Type

Article

Publication Date

2-7-2020

Abstract

All exotoxins exert their action through a primary, specific, or non-specific interaction with certain components of cell membranes. Similar membrane structures may be reconstructed in vitro therefore presenting opportunities for using artificial membrane structures as targets for such toxins. In this endeavor, our investigations focused on employing liposomes as potential tools for toxin removal from biological fluids. For our explorations we chose two potent cytolytic toxins, Streptolysin and Lysenin, which exert their lytic action through direct interaction with membrane components (cholesterol, and sphingomyelin, respectively) resulting in pore assembly. The inserted pores dissipate the transmembrane electrochemical gradients, ultimately leading to cell death. Our studies comprised using Red Blood Cells (RBCs) as target cells since their membrane have large amounts of molecular targets for both toxins and the lytic activity may be easily assessed from estimating the hemoglobin leakage upon exposure to lytic toxins. We used extrusion to prepare unilamellar liposomes as target decoys with size in the range 200-800 nm and containing cholesterol and/or sphingomyelin. Our results show that for both toxins our liposomes may prevent RBC hemolysis when added to the RBC solution before exposure to toxins therefore annihilating the cytolytic activity. Preliminary estimations show that in the case of Streptolysin a single liposome may fully protect up to ∼1 million RBC against lysis, therefore demonstrating a great potential for clinical applications. In the same line, to ensure that the liposomes won’t be rapidly removed by the reticulo-endothelial system, we tested and obtained similar results by employing PEG-ylated (stealth) liposomes as targets. Our work exhibits the great potential of liposomes as a tool for the removal of toxins or viruses from complex biological mixtures.

Comments

This special issue is Supplement 1 of the Biophysical Journal.

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