No abstract

RNA technology has the potential to revolutionize vaccination. However, the lack of clear structure–property relationships in relevant biological models mean there is no clear consensus on the chemical motifs necessary to improve RNA delivery. In this work, we describe the synthesis of a series of copolymers based on the self-hydrolyzing charge-reversible polycation poly­(dimethylaminoethyl acrylate) (pDMAEA), varying the lipophilicity of the additional co-monomers. All copolymers formed stable polyplexes, showing efficient complexation with model nucleic acids from nitrogen/phosphate (N/P) ratios of N/P = 5, with more hydrophobic complexes exhibiting slower charge reversal and disassembly compared to hydrophilic analogues. The more hydrophobic copolymers outperformed hydrophilic versions, homopolymer controls and the reference standard polymer (polyethylenimine), in transfection assays on 2D cell monolayers, albeit with significantly higher toxicities. Similarly, hydrophobic derivatives displayed up to a 4-fold higher efficacy in terms of the numbers of cells expressing green fluorescent protein (GFP+) cells in ex vivo human skin (10%) compared to free RNA (2%), attributed to transfection enrichment in epithelial cells. In contrast, in a mouse model, we observed the reverse trend in terms of RNA transfection, with no observable protein production in more hydrophobic analogues, whereas hydrophilic copolymers induced the highest transfection in vivo. Overall, our results suggest an important relationship between the vector lipophilicity and RNA transfection in vaccine settings, with polymer biocompatibility potentially a key parameter in effective in vivo protein production.

Using a simple dip-coating mechanism, urinary catheters have been coated with poly(2methacryloyloxyethyl)trimethylammonium chloride (pMTAC) using activator regenerated by electron transfer (ARGET)-atom transfer radical polymerization (ATRP). A polydopamine-2-bromoisobutyryl bromide (pDA-BiBBr) initiator was initially grafted to the catheter surface to initiate polymerization resulting in a pDA-g-pMTAC coating. The pDA-g-pMTAC-coated catheters showed a significant reduction in bacterial adhesion, with respect to uncoated silicone catheters, as determined by analyzing microbiological assays as well as scanning electron microscopy images. At the same time, no evidence for cytotoxicity was observed, rather, the coating promoted cell adhesion and proliferation of human cells. This makes the coating attractive for temporary as well as permanently implanted medical devices.Scheme 1 Method for modification of catheter surfaces.Step (i), reaction of BiBBr with DA, followed by polymerization of DA-BiBBr onto the catheter surface.Step (ii), grafting pMTAC to pDA-BiBBr via ARGET-ATRP.This journal is

Biofouling is a serious problem for any wetted structures, having a negative influence on applications as diverse as marine transport, implanted medical devices and water treatment. Here, we address this issue by creating a polydopamine-based coating on desalination reverse osmosis membranes incorporating a bromo-macroinitiator for subsequent polymerisation of sulfobetaine monomers into anti-biofouling polymer brushes. Surface characterisation using attenuated total reflectance-Fourier transform infrared spectroscopy and water contact angle demonstrated the attachment of the polysulfobetaine brushes and that the hydrophilicity increased for the coated membranes. Using a macroinitiator formation time of ten minutes followed by polyzwitterion coating of one hour resulted in a 17% increase in water flux without significant effect on the salt rejection performance. These membranes also exhibited substantial suppression of protein and bacterial attachment of 69% and 88% respectively compared to unmodified membranes.

The emergence of SARS-CoV-2 highlights the global need for platform technologies to enable the rapid development of diagnostics, vaccines, treatments, and personal protective equipment (PPE). However, many current technologies require the detailed mechanistic knowledge of specific material-virion interactions before they can be employed, for example, to aid in the purification of vaccine components or in the design of a more effective PPE. Here, we show that an adaption of a polymer microarray method for screening bacterial-surface interactions allows for the screening of polymers for desirable material-virion interactions. Nonpathogenic virus-like particles including fluorophores are exposed to the arrays in an aqueous buffer as a simple model of virions carried to the surface in saliva/sputum. Competitive binding of Lassa and Rubella virus-like particles is measured to probe the relative binding properties of a selection of copolymers. This provides the first step in the development of a method for the discovery of novel materials with promise for viral binding, with the next being development of this method to assess absolute viral adsorption and assessment of the attenuation of the activity of live virus, which we propose would be part of a material scale up step carried out in high containment facilities, alongside the use of more complex media to represent biological fluids.