Adam L. Sisson

Inhibition of Influenza Virus Activity by Multivalent Glycoarchitectures with Matched Sizes

We describe the synthesis of a series of sialic acid‐conjugated, polyglycerol‐based nanoparticles with diameters in the range of 1–100 nm. Particle sizes were varied along with the degree of functionalization to match the corresponding virus size and receptor multiplicity in order to achieve maximum efficiency. To build up these architectures, we used biocompatible, hyperbranched polyglycerols as scaffolds and recently developed polyglycerol‐based nanogels, the sizes of which can be varied between 2–4 nm and 40–100 nm, respectively. We demonstrate here that such multivalent nanoparticles inhibit influenza A virus cell binding and fusion and consequently infectivity. The potential of multivalency is evident from larger particles showing very efficient inhibition of viral infection up to 80 %. Indeed, both the size of the nanoparticle and the amount of ligand density are important determinants of inhibition efficiency. The inhibitory activity of the tested polymeric nanoparticles drastically increased with size. Particles with similar dimensions to the virus (50–100 nm) are exceedingly effective. We also observed a saturation point in degree of surface functionalization (i.e. ligand density), above which inhibition was not significantly improved. Our study emphasizes the importance of matching particle sizes and ligand densities to mimic biological surfaces and improve interactions; this is a vital concept underlying multivalent interactions.

Polyglycerol nanogels: highly functional scaffolds for biomedical applications

Branched polyglycerols (PGs) are a versatile class of functionalisable, hydrophilic, hydroxylated polyethers with ideal properties for numerous applications. Historically, synthetic limitations have restricted the study of such materials to globular hyperbranched polymers ( 1000 nm). In this Emerging Area minireview we describe how we use miniemulsion polymerisation to prepare polyglycerol nanogels on previously unobtainable length scales. Various cases are discussed with particle sizes that are highly tunable between 25 and 350 nm diameter; methods to surface functionalise such particles are also described. Biodegradable polyglycerol based nanogels have also been prepared by incorporating redox active disulfide branching points within the nanogel structure. Cell culture studies show that these nanogels are highly biocompatible. Additionally, dye labelled nanogels are shown by optical microscopy techniques to readily internalise into cells by endocytic mechanisms. We believe that these polyglycerol nanogels will emerge as excellent materials for use in a broad range of biomedical applications.

Multivalent, biodegradable polyglycerol hydrogels

In this paper we describe the preparation of disulfide crosslinked polyglycerol hydrogels by the ring-opening crosslinking polymerization of glycerol and polyethylene glycol-based polyepoxides and Na2S2. Multivalent polyglycerol hydrogels were prepared by acid-catalyzed hydrolysis of remaining epoxide functionalities. Additionally, a near infrared fluorescent dye was encapsulated in the hydrogel network. Our hydrogels show complete degradation in reducing environments and a controlled release of the fluorescence dye was observed. These hydrogels are interesting scaffolds for bioactive substances, which can be released, triggered by the hydrogel degradation.