Clusters of Nanoscale Liposomes Modulate the Release of Encapsulated Species and Mimic the Compartmentalization Intrinsic in Cell Structures.

Abstract

We report the ability to place a high concentration of liposomes in a confined volume as a multicompartment cluster that mimics biological cells and allows for the modulation of release of encapsulated species. The formation of these coated multicompartmental structures is achieved by first binding liposomes into clusters before encapsulating them within a two-dimensional metal-organic framework composed of tannic acid coordinated with a metal ion. The essential feature is a molecularly thin skin over a ssystem of clustered liposomes in a pouch. The structural features of these pouches are revealed by small-angle scattering and electron microscopy. Through cryogenic electron microscopy, clusters with intact liposomes are observed that appear to be encapsulated within a pouch. Small-angle X-ray scattering shows the emergence of a relatively weak Bragg peak at q = 0.125 Å-1, possibly indicating the attachment of the bilayers of adjacent liposomes. The metal-phenolic network (MPN) forms a nanosized conformal coating around liposome clusters, resulting in the reduced release rate of the encapsulated rhodamine B dye. We further show the possibility of communication between the adjacent nanocompartments in the cluster by demonstrating enhanced energy transfer using fluorescence resonance energy transfer (FRET) experiments where the lipophilic donor dye 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO) incorporated within one liposomal compartment transfers energy upon excitation to the lipophilic acceptor dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) in a neighboring liposomal compartment due to their close proximity within the multicompartmental cluster. These observations have significance in adapting these multicompartmental structures that mimic biological cells for cascade reactions and as new depot drug delivery systems.