Affinity driven molecular transfer from erythrocyte membrane to target cells

A wide variety of antimicrobial peptides are known to bind to - and disrupt microbial plasma membranes. Recently, derivatives of the antimicrobial pep tide dermaseptin S4 were shown to selectively disrupt the plasma membrane o f the intracellular parasite Plasmodium falciparum without harming that of the mammalian host cell, The resulting antimalarial activity is allegedly e xerted after the harmless peptide binding to the membrane of the host cell, followed by peptide translocation across a number of intracellular membran e systems and interaction with that of the intraerythrocyte parasite. In th is study, we present evidence in support of the ability of a membrane-bound peptide, the dermaseptin S4 derivative K-4-S4(1-13)a, to transfer from red blood cells (RBCs) to another distant membrane. Binding of K-4-S4(1-13)a t o the plasma membrane of RBCs was assessed in vitro and in vivo, and found to be rapid, spontaneous and receptor independent, as was the transfer of t he RBC-bound peptide to the plasma membrane of microorganisms. The present study further provides a basis for the possible use of RBCs as a transport vehicle to deliver drugs to distant targets. This drug delivery system invo lves the transient "loading" of RBCs with a lipophilic "hook" peptide. Such a peptide has enough affinity for the RBC's plasma membrane to bind to the membrane, but given the opportunity, the peptide will exit its position an d transfer to another (target) cell for which it has a greater affinity. Th e efficacy of such an affinity driven transfer system was demonstrated expe rimentally by the transfer of K-4-S4(1-13)a from pre-loaded RBCs to bacteri a, yeast and protozoan target cells. (C) 2001 Elsevier Science Inc. All rig hts reserved.