Structure-function relationship of phase-separated liposomes containing diacylglycerol analogues.

The composition and morphology of lipid-based nanoparticles can influence their overall behavior. Previously, we demonstrated that phase separation in liposomes composed of DSPC and a diacylglycerol lipid analogue (DOaG) drives the biodistribution towards a specific subset of endothelial cells in zebrafish embryos. In the absence of traditional targeting functionalities (, antibodies, ligands), this selectivity is mediated solely by the unique liposome morphology and composition, characterized by a DOaG-rich lipid droplet within the DSPC-rich phospholipid bilayer.

Lipid-Based Nanoparticle Functionalization with Coiled-Coil Peptides for and Drug Delivery.

For the delivery of drugs, different nanosized drug carriers (e.g., liposomes, lipid nanoparticles, and micelles) have been developed in order to treat diseases that afflict society.

Deconvolving Passive and Active Targeting of Liposomes Bearing LDL Receptor Binding Peptides Using the Zebrafish Embryo Model.

Improving target versus off-target ratio in nanomedicine remains a major challenge for increasing drug bioavailability and reducing toxicity. Active targeting using ligands on nanoparticle surfaces is a key approach but has limited clinical success. A potential issue is the integration of targeting ligands also changes the physicochemical properties of nanoparticles (passive targeting).

In vitro and in vivo evaluation of clinically-approved ionizable cationic lipids shows divergent results between mRNA transfection and vaccine efficacy.

Ionizable cationic lipids (ICLs) play an essential role in the effectiveness of lipid nanoparticles (LNPs) for delivery of mRNA therapeutics and vaccines; therefore, critical evaluations of their biological performance would extend the existing knowledge in the field. In the present study, we examined the effects of the three clinically-approved ICLs, Dlin-MC3-DMA, ALC-0315 and SM-102, as well as DODAP, on the in vitro and in vivo performance of LNPs for mRNA delivery and vaccine efficacy. mRNA-LNPs containing these lipids were successfully prepared, which were all found to be very similar in their physicochemical properties and mRNA encapsulation efficiencies.

Endocytosis-like DNA uptake by cell wall-deficient bacteria.

Horizontal gene transfer in bacteria is widely believed to occur via conjugation, transduction and transformation. These mechanisms facilitate the passage of DNA across the protective cell wall using sophisticated machinery. Here, we report that cell wall-deficient bacteria can engulf DNA and other extracellular material via an endocytosis-like process.

Selective Disruption of Survivin's Protein-Protein Interactions: A Supramolecular Approach Based on Guanidiniocarbonylpyrrole.

Targeting specific protein binding sites to interfere with protein-protein interactions (PPIs) is crucial for the rational modulation of biologically relevant processes. Survivin, which is highly overexpressed in most cancer cells and considered to be a key player of carcinogenesis, features two functionally relevant binding sites. Here, we demonstrate selective disruption of the Survivin/Histone H3 or the Survivin/Crm1 interaction using a supramolecular approach.

Functional Disruption of the Cancer-Relevant Interaction between Survivin and Histone H3 with a Guanidiniocarbonyl Pyrrole Ligand.

The protein Survivin is highly upregulated in most cancers and considered to be a key player in carcinogenesis. We explored a supramolecular approach to address Survivin as a drug target by inhibiting the protein-protein interaction of Survivin and its functionally relevant binding partner Histone H3. Ligand L1 is based on the guanidiniocarbonyl pyrrole cation and serves as a highly specific anion binder in order to target the interaction between Survivin and Histone H3.

A stimuli responsive two component supramolecular hydrogelator with aggregation-induced emission properties.

In this contribution we describe a novel hydrogelator based on four guadiniumcarbonylpyrrole units in combination with aggregation-induced emission active aromatic thioethers which undergo self-assembly into fibrills in aqueous media as visible in AFM and TEM measurements. These fibrills are weakly luminescent and unable to induce gelation. Upon addition of malonic acid a cross-linking of the single fibres was detected leading to the formation of a highly emissive stable hydrogel.