The successful therapeutic application of small interfering RNA (siRNA) largely relies on the development of safe and effective delivery systems that are able to guide the siRNA therapeutics to the cytoplasm of the target cell. In this report, biodegradable cationic dextran nanogels are engineered by inverse emulsion photopolymerization and their potential as siRNA carriers is evaluated. The nanogels are able to entrap siRNA with a high loading capacity, based on electrostatic interaction. Confocal microscopy and flow cytometry analysis reveal that large amounts of siRNA‐loaded nanogels can be internalized by HuH‐7 human hepatoma cells without significant cytotoxicity. Following their cellular uptake, it is found that the nanogels are mainly trafficked towards the endolysosomes. The influence of two different strategies to enhance endosomal escape on the extent of gene silencing is investigated. It is found that both the application of photochemical internalization (PCI) and the use of an influenza‐derived fusogenic peptide (diINF‐7) can significantly improve the silencing efficiency of siRNA‐loaded nanogels. Furthermore, it is shown that an efficient gene silencing requires the degradation of the nanogels. As the degradation kinetics of the nanogels can easily be tailored, these particles show potential for intracellular controlled release of short interfering RNA.

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Accurate sizing of nanoparticles in biological media is important for drug delivery and biomedical imaging applications since size directly influences the nanoparticle processing and nanotoxicity in vivo. Using fluorescence single particle tracking we have succeeded for the first time in following the aggregation of drug delivery nanoparticles in real time in undiluted whole blood. We demonstrate that, by using a suitable surface functionalization, nanoparticle aggregation in the blood circulation is prevented to a large extent.

Ellagic acid (EA) is a naturally occurring plant polyphenol formed by the hydrolysis of ellagitannins, which are primarily found in grapes, nuts and fruits. EA has been known to have potent anticarcinogenic activities, however, its insolubility under physiological conditions limits its potential applications. In this work, we have prepared complexes of ellagic acid with peptide nanotubes and polycations such as low molecular weight polyethylenimine (PEI), polyarginine and polylysine to enhance its properties for drug delivery. In particular, polycations such as PEI are well known non-viral vectors. Briefly, EA nanofibers were grown by self-assembly and were complexed with peptide nanotubes or poly cations at varying temperature and pH. The formation of the nanocomplexes was confirmed by zeta-potential analysis. The morphologies of the complexes were examined by electron microscopy. Because of the rigid core of EA that offers shape consistence, and the poly-cation shells that passivate the surfaces, coreÀshell nanoconjugates whose average diameters were dependent upon the concentrations and pH were formed. In the formed complexes, the charged amine groups of the polycations most likely interact with the partially deprotonated carboxylate and hydroxyl groups of EA. In some cases, the EA was coupled with rhodamine to examine the effect of bound versus unbound nanocomplexes formed using confocal microscopy. The interactions of the complexes with mammalian cells were examined by live-cell imaging in the presence of normal rat kidney cells. The anticarcinogenic effects of the nanoprobes was explored using HeLa cells. Finally, the ability of the nanocomplexes for drug release was examined at varying pH and concentrations. Such nanocomplexes may have potential applications not only for anticarcinogenic activities but may also help probe mechanisms involved with EA based biodegradable polycationic-based delivery and cellular attachment towards use in varying therapeutic applications.

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