Encapsulation of hydrophobic components in dendrimersomes and decoration of their surface with proteins and nucleic acids

Abstract

Reconstructing the functions of living cells using nonnatural components is one of the great challenges of natural sciences. Compartmentalization, encapsulation, and surface decoration of globular assemblies, known as vesicles, represent key early steps in the reconstitution of synthetic cells. Here we report that vesicles self-assembled from amphiphilic Janus dendrimers, called dendrimersomes, encapsulate high concentrations of hydrophobic components and do so more efficiently than commercially available stealth liposomes assembled from phospholipid components. Multilayer onion-like dendrimersomes demonstrate a particularly high capacity for loading low-molecular weight compounds and even folded proteins. Coassembly of amphiphilic Janus dendrimers with metal-chelating ligands conjugated to amphiphilic Janus dendrimers generates dendrimersomes that selectively display folded proteins on their periphery in an oriented manner. A modular strategy for tethering nucleic acids to the surface of dendrimersomes is also demonstrated. These findings augment the functional capabilities of dendrimersomes to serve as versatile biological membrane mimics.

Nanovesicles displaying functional linear and branched oligomannose self-assembled from sequence-defined Janus glycodendrimers

“…Six cycles of glycosylation and deprotection were repeated to obtain the desired hexa-saccharide. Upon completion of the assembly, the compound was cleaved form the solid support and subjected to Zemplèn methanolysis and hydrogenolysis to give compound hexaMan (13). The AGA of oligoMan is usually performed on a 0.0125mmol scale and therefore requires a highly efficient methodology to conjugate this small quantity of oligosaccharides to the JGDs.…”

“…These vesicles are denoted as liposomes, polymersomes, and dendrimersomes (DSs), respectively. Synthetic amphiphilic JDs, constructed by orthogonal coupling of hydrophobic and hydrophilic dendrons, mimic phospholipids and self-assemble into stable DSs in water, buffer, and serum (8)(9)(10)(11)(12)(13). DSs have a membrane thickness similar to phospholipids (∼4 nm) (9,10), which facilitated the development of hybrid vesicles from JDs with both bacteria and human cell membranes to transplant the components of the natural membranes into the membranes of the hybrid synthetic cells (11,12).…”

“…DSs have a membrane thickness similar to phospholipids (∼4 nm) (9,10), which facilitated the development of hybrid vesicles from JDs with both bacteria and human cell membranes to transplant the components of the natural membranes into the membranes of the hybrid synthetic cells (11,12). DSs are very efficient for the encapsulation of hydrophobic organic molecules, including dyes and proteins (13). More recently, Janus glycodendrimers (JGDs) (14), the sugar-conjugated analogs of JDs, were designed to mimic glycolipids.…”

Merging Macromolecular and Supramolecular Chemistry into Bioinspired Synthesis of Complex Systems

“…Recently self‐assembling amphiphilic Janus dendrimers and Janus glycodendrimers have been discovered to self‐assemble by simple injection from an organic solvent such as ethanol into water or buffer into monodisperse vesicles with predictable dimensions named dendrimersomes and glycodendrimersomes exhibiting similar bilayer thickness with that of natural cell membranes –. They can be co‐assembled with bacterial and mammalian cell membranes and their engineered surface can generate rafts that are accessible for structural analysis by diffraction and diffraction‐like methods –…”

Interaction of polyamidoamine dendrimers and amphiphylic dendrons with lipid membranes

“…В работе [44] изучена способность амфифильных дендримеров, формирующих дендримерсомы, инкапсулировать высокие концентрации гидрофобных компонентов, при этом более эффективно, чем коммерчески доступные липосомы, собранные из фосфолипидных компонентов. Многослойные луковичные дендримерсомы демонстрировали особенно высокую способность загружать низкомолекулярные соединения и даже свернутые белки.…”