Self-assembly of amphiphilic Janus dendrimers into uniform onion-like dendrimersomes with predictable size and number of bilayers

Abstract

A constitutional isomeric library synthesized by a modular approach has been used to discover six amphiphilic Janus dendrimer primary structures, which self-assemble into uniform onion-like vesicles with predictable dimensions and number of internal bilayers. These vesicles, denoted onion-like dendrimersomes, are assembled by simple injection of a solution of Janus dendrimer in a water-miscible solvent into water or buffer. These dendrimersomes provide mimics of double-bilayer and multibilayer biological membranes with dimensions and number of bilayers predicted by the Janus compound concentration in water. The simple injection method of preparation is accessible without any special equipment, generating uniform vesicles, and thus provides a promising tool for fundamental studies as well as technological applications in nanomedicine and other fields.synthetic membranes | biomembrane mimics | multibilayer vesicles M ost living organisms contain single-bilayer membranes composed of lipids, glycolipids, cholesterol, transmembrane proteins, and glycoproteins (1). Gram-negative bacteria (2, 3) and the cell nucleus (4), however, exhibit a strikingly special envelope that consists of a concentric double-bilayer membrane. More complex membranes are also encountered in cells and their various organelles, such as multivesicular structures of eukaryotic cells (5) and endosomes (6), and multibilayer structures of endoplasmic reticulum (7,8), myelin (9, 10), and multilamellar bodies (11,12). This diversity of biological membranes inspired corresponding biological mimics. Liposomes ( Fig. 1) self-assembled from phospholipids are the first mimics of singlebilayer biological membranes (13-16), but they are polydisperse, unstable, and permeable (14). Stealth liposomes coassembled from phospholipids, cholesterol, and phospholipids conjugated with poly(ethylene glycol) exhibit improved stability, permeability, and mechanical properties (17)(18)(19)(20). Polymersomes (21-24) assembled from amphiphilic block copolymers exhibit better mechanical properties and permeability, but are not always biocompatible and are polydisperse. Dendrimersomes (25-28) self-assembled from amphiphilic Janus dendrimers and minidendrimers (26-28) have also been elaborated to mimic single-bilayer biological membranes. Amphiphilic Janus dendrimers take advantage of multivalency both in their hydrophobic and hydrophilic parts (23,(29)(30)(31)(32). Dendrimersomes are assembled by simple injection (33) of a solution of an amphiphilic Janus dendrimer (26) in a water-soluble solvent into water or buffer and produce uniform (34), impermeable, and stable vesicles with excellent mechanical properties. In addition, their size and properties can be predicted by their primary structure (27). Amphiphilic Janus glycodendrimers self-assemble into glycodendrimersomes that mimic the glycan ligands of biological membranes (35). They have been demonstrated to be bioactive toward biomedically relevant bacterial, plant, and human lectins, and could have numerous applications i...

Onion-like glycodendrimersomes from sequence-defined Janus glycodendrimers and influence of architecture on reactivity to a lectin

“…Indeed, for various types of lectins, this surface design has been found to be inert (16,(27)(28)(29). Also, the presence of methoxytriethoxy has previously been shown to be conducive to the formation of onionlike dendrimersomes (3). This result prompted the use of Janus GDs as building blocks for obtaining onion-like GDSs.…”

Bioactive cell-like hybrids coassembled from (glyco)dendrimersomes with bacterial membranes

“…Four JDs were selected from 19 libraries containing 144 compounds ( Fig. 2) (9,24,26,36). JD-1, JD-2, and JD-3 are twin-twin molecules (9, 24) containing twin-hydrophobic and twin-hydrophilic dendrons, whereas JD-4 is a single-single compound (26) based on single-hydrophobic and single-hydrophilic dendrons.…”

Novel stable dendrimersome formulation for safe bioimaging applications

“…mechanical resistance, wall thickness, chemical groups exposed on the outer surface) has driven the search for new categories of amphiphiles other than phospholipids. [10][11][12] Two examples are represented by polymersomes [13][14][15] and dendrimersomes, [16][17][18][19][20][21][22] which are obtained through the self-assembly of amphiphilic block co-polymers or JDs, respectively. Whereas the potential of polymersomes in biomedical studies has been already demonstrated, 14,15 dendrimersomes have been proposed only very recently, and therefore their behaviour in biological environments is largely unexplored.…”