Semantic Priming of Colored Signs in the Peripheral Vision during Electronic Text Reading

This study explores if peripheral colored ambient light or colored light can be noticed and semantically associated with text while reading a novel from an Electronic Visual Display (EVD). Additionally, it is investigated if those colored signs are perceived as supplementary to the story and result in a more immersive experience. For that purpose, a user evaluation study was performed based on attention theory (selective attention, semantic priming, and divided attention), reading behavior, and semantics of colors. Participants received a reading assignment. While reading a novel from an e-book, dynamic colored ambient light or colored light was emitted. Throughout the reading assignment, the colors were adapted to the particular scenes the participant was reading. Findings suggest that attention can be divided between reading the novel from an EVD and the ambient color signs

Modular Synthesis of Bioreducible Gene Vectors through Polyaddition of N,N′-Dimethylcystamine and Diglycidyl Ethers

Bioreducible, cationic linear poly(amino ether)s (PAEs) were designed as promising gene vectors. These polymers were synthesized by the reaction of a disulfide-functional monomer, N,N′-dimethylcystamine (DMC), and several different diglycidyl ethers. The resulting PAEs displayed a substantial buffer capacity (up to 64%) in the endosomal acidification region of pH 7.4–5.1. The PAEs condense plasmid DNA into 80–200 nm sized polyplexes, and have surface charges ranging from +20 to +40 mV. The polyplexes readily release DNA upon exposure to reducing conditions (2.5 mM DTT) due to the cleavage of the disulfide groups that is present in the main chain of the polymers, as was demonstrated by agarose gel electrophoresis. Upon exposing COS-7 cells to polyplexes that were prepared at polymer/DNA w/w ratios below 48, cell viabilities between 80–100% were observed, even under serum-free conditions. These polyplexes show comparable or higher transfection efficiencies (up to 38%) compared to 25 kDa branched polyethylenimine (PEI) polyplexes (12% under serum-free conditions). Moreover, the PAE-based polyplexes yield transfection efficiencies as high as 32% in serum-containing medium, which makes these polymers interesting for gene delivery applications

Thiourea-functional bioreducible poly(amido amine)s in gene delivery

Successful gene therapy relies on gene delivery vectors with high transfection efficiency and minimal toxicity. Bioreducible cationic polymers were developed as nonviral gene delivery vectors due to their large capacity to carry genes and highly modular synthesis. Poly(amido amine)s (PAAs) with disulfide linkages along the backbone and varying amounts of thiourea moieties in the side-chains were prepared via Michael-type polyaddition of 1-(4-aminobutyl)-3-(pyridin-3-yl)thiourea to N,N'-cystamine bisacrylamide (CBA). The thiourea-containing PAAs are able to condensate plasmid DNA into nanosized polyplexes with positive surface charge as determined by dynamic light scattering and zeta-potential measurements. The plasmid DNA is readily liberated from the polyplexes upon exposure to reducing environment, as confirmed by gel electrophoresis after treatment with the reducing agent dithiothreitol. Polyplexes of thiourea-functionalized PAAs show no discernible toxicity and markedly higher transfection efficiencies on COS-7 cells as compared to polyplexes of the frequently applied branched polyethylenimine (PEI, 25 kDa), as well as the PAA analogue obtained via polyaddition of 1-amino-4-butanol (ABOL) to CBA (pABOL), at their optimal transfection conditions. The high transfection capacity of the thiourea-functionalized PAAs remains largely unaffected in the presence of 10% serum, while the transfection efficiencies of PEI and pABOL are considerably reduced under these conditions. The results demonstrate the potential of thiourea functionalization of PAAs in enhancing their transfection efficiencies while maintaining minimal toxicities

Responsive crosslinked polymer nanogels for imaging and therapeutics delivery

Water-soluble, nano-sized crosslinked polymer networks, or nanogels, are delivery vehicles, which have highly interesting properties for therapeutic delivery and imaging. Nanogels may also possess responsive properties, depending on the employed polymers, allowing controlled release of therapeutics or image contrast generation upon exposure to physical or (bio)chemical cues. In this review, polymer nanogels are explored for application in imaging as well as for controlled drug and gene delivery. Moreover, nanogels are explored as responsive biomaterials and future applications are highlighted

Disulfide-functional poly(amido amine)s with tunable degradability for gene delivery

Controlled degradability in response to the local environment is one of the most effective strategies to achieve spatiotemporal release of genes from a polymeric carrier. Exploiting the differences in reduction potential between the extracellular and intracellular environment, disulfides are frequently incorporated into the backbone of polymeric drug delivery agents to ensure efficient intracellular release of the payload. However, although to a lesser extent, reduction of disulfides may also occur in the extracellular environment and should be prevented to avoid premature release. Accurate control over the stability of disulfide linkages enables the optimization of polymeric carriers for efficient drug delivery. Bioreducible poly(amido amine)s (PAAs) with varying degrees of steric hindrance adjacent to the disulfide bonds (0, 2 or 4 methyl groups) were prepared in order to obtain carriers with controlled stability. The degradation behavior of these PAA-polymers was evaluated under different reducing conditions and their in vitro toxicities and transfection efficiencies were assessed. Degradation of the PAA-based polyplexes consistently required higher reducing strengths as the steric hindrance near the disulfide bonds increased. Polyplexes based on 2-methyl cystamine disulfide based PAA polymer (PAA2m) remained stable under extracellular glutathione concentrations (0.001–0.01 mM), while degrading within 1 h under reducing conditions similar to those in the intracellular environment (1–10 mM glutathione). This polymer exhibited excellent transfection capabilities, with efficiencies up to 90% of transfected cells. PAA0m showed slightly reduced transfection properties compared to PAA2m, likely due to premature degradation. The severely hindered PAA4m, however, displayed increased toxicity, accompanied by reduced transfection efficiency, as a result of its exceptional stability. These results demonstrate the feasibility of introducing steric hindrance near the disulfide moiety to tune polyplex stability against bioreduction, and show that PAA2m is a promising polymer to be further developed for gene therapy

Linear Poly(ethylenimine-propylenimine) Random Copolymers for Gene Delivery: From Polymer Synthesis to Efficient Transfection with High Serum Tolerance

Naturally occurring oligoamines, such as spermine, spermidine, and putrescine, are well-known regulators of gene expression. These oligoamines frequently have short alkyl spacers with varying lengths between the amines. Linear polyethylenimine (PEI) is a polyamine that has been widely applied as a gene vector, with various formulations currently in clinical trials. In order to emulate natural oligoamine gene regulators, linear random copolymers containing both PEI and polypropylenimine (PPI) repeat units were designed as novel gene delivery agents. In general, statistical copolymerization of 2-oxazolines and 2-oxazines leads to the formation of gradient copolymers. In this study, however, we describe for the first time the synthesis of near-ideal random 2-oxazoline/2-oxazine copolymers through careful tuning of the monomer structures and reactivity as well as polymerization conditions. These copolymers were then transformed into near-random PEI-PPI copolymers by controlled side-chain hydrolysis. The prepared PEI-PPI copolymers formed stable polyplexes with GFP-encoding plasmid DNA, as validated by dynamic light scattering. Furthermore, the cytotoxicity and transfection efficiency of polyplexes were evaluated in C2C12 mouse myoblasts. While the polymer chain length did not significantly increase the toxicity, a higher PPI content was associated with increased toxicity and also lowered the amount of polymers needed to achieve efficient transfection. The transfection efficiency was significantly influenced by the degree of polymerization of PEI-PPI, whereby longer polymers resulted in more transfected cells. Copolymers with 60% or lower PPI content exhibited a good balance between high plasmid-DNA transfection efficiency and low toxicity. Interestingly, these novel PEI-PPI copolymers revealed exceptional serum tolerance, whereby transfection efficiencies of up to 53% of transfected cells were achieved even under 50% serum conditions. These copolymers, especially PEI-PPI with DP500 and a 1:1 PEI/PPI ratio, were identified as promising transfection agents for plasmid DNA