Polymeric materials provide particularly attractive scaffolds for the creation of supramolecular bioconjugates for the delivery of nucleic acids but typically lack the efficiency and biocompatibility to be clinically relevant. To address both issues, we produced zwitterion-like derivatives of polyethylenimine via succinylation of primary and secondary amines (zPEI). Polymers were generated with 9−55% of the amines modified (zPEI X, where X indicates the percentage of amines succinylated). Characterization of polymer/DNA interactions revealed that the presence of succinyl groups decreased the protonation constant of zPEI, resulting in both a decreased buffering capacity and polyplexes that dissociated in the presence of lower amounts of a competing counteranion compared to unmodified PEI. zPEI polyplexes also exhibited decreased aggregation in the presence of serum proteins. In the absence of serum, transfections with zPEI/DNA polyplexes exhibited similar or slightly improved transgene expression compared to unmodified PEI/DNA polyplexes. More importantly, zPEI 9−25 increased transgene expression up to 51-fold upon transfection in the presence of serum compared to PEI/DNA, while higher succinylation decreased gene delivery activity. Gene delivery mediated by zPEI 9/DNA polyplexes in the presence of serum was equal to or greater than unmodified PEI/DNA polyplexes in the absence of serum. The data suggest that succinylation increased gene transfection by decreasing polymer/DNA interaction strength, which may allow for more facile polyplex unpackaging, and/or increased stability of polyplex size and inhibition of aggregation in the presence of serum. However, it appears there exists a balance between the positive effects of succinylation and the need for sufficient polymer/DNA binding to condense and protect the cargo.

All biogels are heterogeneous, consisting of functional groups with different biophysical properties arrayed on spatially disordered polymer networks. Nanoparticles diffusing in such biogels experience a mixture of attractive and repulsive interactions. Here, we present experimental and theoretical studies of charged particle diffusion in gels with a random distribution of attractive and repulsive electrostatic interaction sites inside the gel. In addition to interaction disorder, we theoretically investigate the effect of spatial disorder of the polymer network. Our coarse-grained simulations reveal that attractive interactions primarily determine the diffusive behavior of the particles in systems with mixed attractive and repulsive interactions. As a consequence, charged particles of either sign are immobilized in mixed cationic/anionic gels because they are trapped near oppositely charged interaction sites, whereas neutral particles diffuse rapidly. Even small fractions of oppositely charged interaction sites lead to strong trapping of a charged particle. Translational diffusion coefficients of charged probe molecules in gels consisting of mixed cationic and anionic dextran polymers are determined by fluorescence correlation spectroscopy and quantitatively confirm our theoretical predictions.

Foams prepared from vinylbenzyl chloride and crosslinked with divinylbenzene were functionalized with trialkylphosphite and tetralkylvinylidene diphosphonate. It was determined that the foams could be uniformly functionalized. Batch studies with the functionalized foams show that high levels of metal ion complexation can be achieved. Foams may therefore offer an important alternative to beads for rapid complexation reactions due to their highly porous structure.

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