Modulating efficacy and cytotoxicity of lipoamino fatty acid nucleic acid carriers using disulfide or hydrophobic spacers.

Double pH-responsive xenopeptides comprising polar ionizable succinoyl tetraethylene pentamine (Stp) motifs and lipophilic ionizable lipoamino fatty acids (LAFs) were recently found to efficiently transfect mRNA and pDNA at low doses. However, potency was often accompanied with cytotoxicity at higher doses. Insertion of bioreducible disulfide building blocks (ssbb) or non-reducible hydrophobic spacers between polar and apolar ionizable domains of LAF-Stp carriers should mitigate toxicity of xenopeptides.

In Vivo Endothelial Cell Gene Silencing by siRNA-LNPs Tuned with Lipoamino Bundle Chemical and Ligand Targeting.

Although small-interfering RNAs (siRNAs) are specific silencers for numerous disease-related genes, their clinical applications still require safe and effective means of delivery into target cells. Highly efficient lipid nanoparticles (LNPs) are developed for siRNA delivery, showcasing the advantages of novel pH-responsive lipoamino xenopeptide (XP) carriers. These sequence-defined XPs are assembled by branched lysine linkages between cationizable polar succinoyl tetraethylene pentamine (Stp) units and apolar lipoamino fatty acids (LAFs) at various ratios into bundle or U-shape topologies.

Receptor-Targeted Carbon Nanodot Delivery through Polymer Caging and Click Chemistry-Supported LRP1 Ligand Attachment.

Carbon nanodots present resistance to photobleaching, bright photoluminescence, and superior biocompatibility, making them highly promising for bioimaging applications. Herein, nanoprobes were caged with four-armed oligomers and subsequently modified with a novel DBCO-PEG-modified retro-enantio peptide ligand reL57, enhancing cellular uptake into U87MG glioma cells highly expressing low-density lipoprotein receptor-related protein 1 (LRP1). A key point in the development of the oligomers was the incorporation of ε-amino-linked lysines instead of standard α-amino-linked lysines, which considerably extended the contour length per monomer.

Novel concept suppressing plasma heat pulses in a tokamak by fast divertor sweeping.

One of the remaining challenges in magnetic thermonuclear fusion is survival of the heat shield protecting the tokamak reactor vessel against excessive plasma heat fluxes. Unmitigated high confinement edge localized mode (ELM) is a regular heat pulse damaging the heat shield. We suggest a novel concept of magnetic sweeping of the plasma contact strike point fast and far enough in order to spread this heat pulse.

Integrated bioelectronic proton-gated logic elements utilizing nanoscale patterned Nafion.

A central endeavour in bioelectronics is the development of logic elements to transduce and process ionic to electronic signals. Motivated by this challenge, we report fully monolithic, nanoscale logic elements featuring n- and p-type nanowires as electronic channels that are proton-gated by electron-beam patterned Nafion. We demonstrate inverter circuits with state-of-the-art ion-to-electron transduction performance giving DC gain exceeding 5 and frequency response up to 2 kHz.