Publications by authors named "Thomas H Kissel"
Time-resolved quantitative colocalization analysis is a method based on confocal fluorescence microscopy allowing for a sophisticated characterization of nanomaterials with respect to their intracellular trafficking. This technique was applied to relate the internalization patterns of nanoparticles i.e.
View Article and Find Full Text PDFPolymeric non-viral vector systems for pulmonary application of siRNA are promising carriers, but have failed to enter clinical trials because of safety and efficiency problems. Therefore, improving their transfection efficiency, as well as their toxicological profile, is the subject of intensive research efforts. Six different poly(ethylene imine) (PEI)-based nanocarriers, with hydrophilic and hydrophobic PEG modifications, were toxicologically evaluated for pulmonary application in mice.
View Article and Find Full Text PDFAmphiphilic PEG-PCL-PEI triblock copolymers self-assemble into nano-scaled, positively charged, multifunctional carriers, suitable for drug and gene delivery. A set of block copolymers with varying hydrophilic/hydrophobic ratio (systematically altered at the borderline of micelle and particle forming polymers) was synthesized, characterized and assembled into carriers. A detailed structural characterization in the liquid state of these assemblies was carried out: carrier size was determined using dynamic light scattering, cryogenic scanning electron microscopy and atomic force microscopy.
View Article and Find Full Text PDFArticle Synopsis
- The study explores off-target effects of non-viral siRNA delivery, focusing on the toxicity mechanisms of different polymer-based transfection agents like PEI and PEG-PEI.
- PEG-PEI, typically seen as safer, was found to induce apoptosis variably depending on the cell line and concentration, suggesting that polymeric vectors can have unpredictable biological responses.
- Results indicate that the activation of gene expression by the delivery polymers can interfere with gene-silencing outcomes, highlighting the need for understanding these effects to improve the design of safer, more effective RNAi delivery systems.
Purpose: The objective of this study was to investigate how the degree of amine substitution of amine-modified poly(vinyl alcohol) (PVA) affects complexation of siRNA, protection of siRNA against degrading enzymes, intracellular uptake and gene silencing.
Methods: A series of DEAPA-PVA polymers with increasing amine density was synthesized by modifying the hydroxyl groups in the PVA backbone with diethylamino propylamine groups using CDI chemistry. These polymers were characterized with regard to their ability to complex and protect siRNA against RNase.