Supramolecular Double Helices from Small C-Symmetrical Molecules Aggregated in Water.

Supramolecular fibers in water, micrometers long and several nanometers in width, are among the most studied nanostructures for biomedical applications. These supramolecular polymers are formed through a spontaneous self-assembly process of small amphiphilic molecules by specific secondary interactions. Although many compounds do not possess a stereocenter, recent studies suggest the (co)existence of helical structures, albeit in racemic form.

Supramolecular Copolymerization as a Strategy to Control the Stability of Self-Assembled Nanofibers.

A major challenge in supramolecular polymerization is controlling the stability of the polymers formed, that is, controlling the rate of monomer exchange in the equilibrium between monomer and polymer. The exchange dynamics of supramolecular polymers based on benzene-1,3,5-tricarboxamide (BTA) can be regulated by copolymerizing molecules with dendronized (dBTA) and linear (nBTA) ethylene glycol-based water-soluble side chains. Whereas nBTAs form long nanofibers in water, dBTAs do not polymerize, forming instead small spherical aggregates.

Aggregation Behavior of Non-ionic Twinned Amphiphiles and Their Application as Biomedical Nanocarriers.

A new class of twinned amphiphiles was developed by conjugating a pair of hydrophilic head groups from mPEG chains (M : 350 or 1000) and a pair of hydrophobic segments from linear alkyl chains (C or C ) through a novel spacer synthesized from glycerol and p-hydroxybenzoic acid. The aggregation phenomena of the amphiphiles were proven by DLS and fluorescence experiments, whereas size and morphology of the aggregates were evaluated by cryo-TEM. The measurements proved the formation of globular, thread-like or rod-like micelles as well as planar double-layer assemblies, depending on the amphiphile's molecular structure.

Crosslinked Redox-Responsive Micelles Based on Lipoic Acid-Derived Amphiphiles for Enhanced siRNA Delivery.

Successful application of gene silencing approaches critically depends on systems that are able to safely and efficiently deliver genetic material such as small interfering RNA (siRNA). Due to their beneficial well-defined dendritic nanostructure, self-assembling dendrimers are emerging as promising nanovectors for siRNA delivery. However, these kinds of vectors are plagued with stability issues, especially when considered for in vivo applications.

Supramolecular Architectures of Dendritic Amphiphiles in Water.

Dendritic molecules are an exciting research topic because of their highly branched architecture, multiple functional groups on the periphery, and very pertinent features for various applications. Self-assembling dendritic amphiphiles have produced different nanostructures with unique morphologies and properties. Since their self-assembly in water is greatly relevant for biomedical applications, researchers have been looking for a way to rationally design dendritic amphiphiles for the last few decades.

Optimized effective charge density and size of polyglycerol amines leads to strong knockdown efficacy in vivo.

RNA interference (RNAi)-based therapy extends the range of "druggable" targets beyond existing pharmacological drugs and enables the development of new treatment strategies for various diseases. A prerequisite are non-viral polyvalent gene delivery vectors capable for safe and effective siRNA delivery to cells in vivo allowing a broad clinical application. We synthesized hyperbranched polyglycerol amines (hPG amines) which varied in their charge density, multiplicity (absolute frequency of amine groups) and core size to successfully develop potent and safe siRNA transfer vectors.

Dendronylation: Residue-specific chemoselective attachment of oligoglycerol dendrimers on proteins with noncanonical amino acids.

Polyglycerol dendrimers as an important class of polymeric materials especially attractive for covalent attachment to therapeutic proteins as a useful alternative to traditional PEGylation procedures. Herein, we combine in vivo noncanonical amino acid (ncAA) incorporation and chemoselective conjugation in vitro to produce novel hybrid protein-dendrimer conjugates with the defined architectures. We incorporated Azidohomoalanine (Aha) as methionine substitute in vivo into various protein scaffolds to allow non-invasive dendrimer conjugations (dendronylation).

Systematic adjustment of charge densities and size of polyglycerol amines reduces cytotoxic effects and enhances cellular uptake.

Excessive cationic charge density of polyplexes during cellular uptake is still a major hurdle in the field of non-viral gene delivery. The most efficient cationic vectors such as polyethylene imine (PEI) or polyamidoamine (PAMAM) can be highly toxic and may induce strong side effects due to their high cationic charge densities. Alternatives like polyethylene glycol (PEG) are used to 'shield' these charges and thus to reduce the cytotoxic effects known for PEI/PEG-core-shell architectures.

Online monitoring the isomerization of an azobenzene-based dendritic bolaamphiphile using ion mobility-mass spectrometry.

Ion mobility-mass spectrometry was used to obtain detailed information about the kinetics of the light-induced cis/trans isomerization process of a new supramolecular azobenzene-based bolaamphiphile. Further experiments revealed that the investigated light-induced structural transition dramatically influences the aggregation behaviour of the molecule.

Towards engineering of self-assembled nanostructures using non-ionic dendritic amphiphiles.

Engineering nanostructures of defined size and morphology is a great challenge in the field of self-assembly. Herein we report on the formation of supramolecular nanostructures of defined morphologies with subtle structural changes for a new series of dendritic amphiphiles. Subsequently, we studied their application as nanocarriers for guest molecules.

Dendritic core-shell systems as soft drug delivery nanocarriers.

Unimolecular micelles are covalently bound molecular architectures and therefore highly stable which makes them particularly attractive for drug delivery. Accordingly, many reports in the literature emphasize the importance of these molecular architectures for nanomedicine. This conceptual review will present some of the recent advances in the application of these dendritic core-shell systems for drug delivery.

Carbon-based cores with polyglycerol shells - the importance of core flexibility for encapsulation of hydrophobic guests.

Two core-shell nanoparticles with polyglycerol shells and sp carbon cores with different flexibilities (soft dendritic polyethylene and hard nanodiamond) were synthesized, their encapsulation capacities were compared, and their ability to transport into tumor cells was investigated. The nanocarrier with a soft core was superior to the hard one.