A new fluorescent dye for cell tracing and mitochondrial imaging in vitro and in vivo.

Mitochondria contribute to redox and calcium balance, and apoptosis thus regulating cellular fate. In the present study, mitochondrial staining applying a novel dye, V07-07059, was performed in human embryonic kidney cells, a human vascular endothelial cell line and primary human mononuclear cells. The new fluorescent mega Stokes dye (peak excitation: 488 nm, peak emission: 554 nm) showed superior fluorescent properties and stability.

The influence of polymer architecture on in vitro pDNA transfection.

In 2012, the first gene therapy agent was approved by the Europe Medicines Agency leading to increased interest in this research field. Beside viruses, non-viral agents based on lipids or polymers represent aspiring alternatives to deliver the genetic material. Different hurdles have to be overcome depending on the kind of nucleic acid used, where plasmid DNA (pDNA) and small interfering RNA represent the common ones.

Comparison of the uptake of methacrylate-based nanoparticles in static and dynamic in vitro systems as well as in vivo.

Polymer-based nanoparticles are promising drug delivery systems allowing the development of new drug and treatment strategies with reduced side effects. However, it remains a challenge to screen for new and effective nanoparticle-based systems in vitro. Important factors influencing the behavior of nanoparticles in vivo cannot be simulated in screening assays in vitro, which still represent the main tools in academic research and pharmaceutical industry.

A cationic poly(2-oxazoline) with high in vitro transfection efficiency identified by a library approach.

To date, cationic polymers with high transfection efficiencies (TE) often have a high cytotoxicity. By screening an 18-membered library of cationic 2-oxazoline-based polymers, a polymer with similar TE as linear poly(ethylene imine) but no detectable cytotoxicity at the investigated concentrations could be identified. The influence of the polymer side chain hydrophobicity and the type and content of amino groups on the pDNA condensation, the TE, the cytotoxicity, the cellular membrane interaction as well as the size, charge, and stability of the polyplexes was studied.

Small but powerful: co-assembly of polyether-based triblock terpolymers into sub-30 nm micelles and synergistic effects on cellular interactions.

We introduce a versatile ABC triblock terpoly- mer platform based on poly(ethylene oxide)-block-poly(allyl glycidyl ether)-block-poly(tert-butyl glycidyl ether) (PEO-b-PAGE-b-PtBGE) and subsequent functionalization of the PAGE segment with thiogalactose (hydroxyl), cysteamine (amino), and 2-mercaptopropionic acid (carboxy) by thiol-ene chemistry. These materials are used to prepare core-shell-corona micelles with a PtBGE core, a PAGE shell, and a PEO corona and sizes below 30 nm in aqueous media. We investigate the influence of different functional groups on micelle formation and cellular uptake.

A paradigm change: efficient transfection of human leukemia cells by stimuli-responsive multicompartment micelles.

The controlled nonviral delivery of genetic material using cationic polymers into cells has been of interest during the past three decades, yet the ideal delivery agent featuring utmost transfection efficiency and low cytotoxicity still has to be developed. Here, we demonstrate that multicompartment micelles from stimuli-responsive triblock terpolymers, polybutadiene-block-poly(methacrylic acid)-block-poly(2-(dimethylamino)ethyl methacrylate) (BMAAD), are promising candidates. The structures exhibit a patchy shell, consisting of amphiphilic (interpolyelectrolyte complexes, MAA and D) and cationic patches (excess D), generating a surface reminiscent to those of certain viruses and capable of undergoing pH-dependent changes in charge stoichiometry.

Parallel high-throughput screening of polymer vectors for nonviral gene delivery: evaluation of structure-property relationships of transfection.

In recent years, "high-throughput" (HT) has turned into a keyword in polymer research. In this study, we present a novel HT workflow for the investigation of cationic polymers for gene delivery applications. For this purpose, various poly(ethylene imine)s (PEI) were used as representative vectors and investigated via HT-assays in a 96-well plate format, starting from polyplex preparation up to the examination of the transfection process.