The water exchange process that transfers the paramagnetic effect of MRI contrast agents to the bulk water pool is fundamental for contrast enhancement.  Nanosized carrier systems such as liposomes are often used to deliver a large payload of paramagnetic contrast agents in order to increase the local concentration of the imaging agent for molecular imaging applications.  The major disadvantage of core encapsulated liposomal MRI contrast agents has been the relaxivity quenching due to the slow diffusion rate of water molecules across the lipid bilayer.  The goal of this project was to engineer nanosized, �smart� MRI contrast agents which consist of a Gd-complex encapsulated within stealth liposomal vesicles. The water exchange rate through the lipid bilayer will be regulated by the opening and closing of chemically modified bacterial mechanosensitive (MscL) channels. A mutant MscL channel whose gating could be controlled by chemical modification in the pore was reconstituted into Gd-DOTA loaded liposomes.  After treatment with a reagent (MTSET) that introduces charges in the pore, the relaxivity of the proteoliposomes was increased to values similar to that of the liposomes lysed with Triton. When channels modified with a pH sensitive functional group were reconstituted in the liposomes, the relaxivity of Gd-loaded liposomes significantly increased when the pH was adjusted to 6 from 8 demonstrating that the protein channel could be used to control water exchange rate across the lipid bilayer.

Controlling the relaxivity of liposomal MRI agents through the gating of a mechanosensitive bacterial channel

247th National Meeting (2014)

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