Simon F. R. Hinkley

The ongoing COVID-19 pandemic, caused by SARS-CoV-2, continues to pose major global health challenges despite extensive vaccination efforts. Variant escape, waning immunity, and reduced vaccine efficacy in immunocompromised populations underscore the urgent need for complementary antiviral therapeutics. Here, we report the design, synthesis, and biological evaluation of precision-engineered dermatan sulfate (DS)-mimetic glycopolymers as multi-targeted inhibitors of SARS-CoV-2. Guided by molecular docking and virtual screening, sulfation at the C2 and C4 positions of iduronic acid was identified as critical for binding to the viral spike protein and inhibiting host and viral enzymes, including heparanase (HPSE) and main protease (M^pro). Chemically synthesized DS disaccharides were covalently grafted onto polymer scaffolds via a post-modification strategy, yielding glycopolymers with well-defined assembly that form uniform nanoparticles under physiological conditions. Surface plasmon resonance and pseudovirus assays revealed strong binding to the viral spike protein (K_D ≈ 177 nM), potent viral neutralization, and minimal cytotoxicity. Cellular uptake studies further demonstrated efficient internalization of nanoparticles and intracellular inhibition of HPSE and M^pro. These results establish a modular, non-anticoagulant, and glycosaminoglycan-mimetic platform for the development of broad-spectrum antiviral agents to complement vaccination and enhance preparedness against emerging coronavirus variants.

Stroke remains a leading cause of adult disability, driven in part by the formation of a non-permissive extracellular matrix environment that limits endogenous repair. Injectable biomaterials that can modulate this microenvironment while enabling localised therapeutic delivery, represent a promising strategy for post-stroke brain regeneration. Here, we report the development of a thermoresponsive hybrid hydrogel composed of chitosan, β-glycerophosphate, silk fibroin, polyvinyl alcohol and polyvinyl pyrrolidone, engineered to provide a tuneable physicochemical properties and enhanced biological functionalities for intracerebral delivery. Systemic optimisation identified a formulation (F6) that exhibited rapid gelation at physiological temperature, appropriate viscoelastic properties, a microporous architecture, and controlled biodegradation, conducive to cellular infiltration and molecular transport. In a mouse model of photothrombotic stroke, intracerebral delivery of the F6 hydrogel attenuated reactive astrogliosis and microglial activation in the peri-infarct region, while enhancing neurogenesis in the subventricular zone. Notably, incorporation of brain-derived neurotrophic factor within the hydrogel significantly improved functional recovery over 8 weeks, demonstrating the capacity of this system to act as a localised delivery platform for neuro-regenerative therapeutics. Together, this study establishes a tuneable thermoresponsive hydrogel platform that integrates structural support with controlled therapeutic delivery, highlighting its potential as a minimally invasive strategy for modulating the post-stroke microenvironment and promoting functional recovery.

Copper and copper-based compounds have broad spectrum antimicrobial activity, but concerns about leaching into the environment and toxicity on non-target organisms is leading the use of copper-based coatings being restricted. Our objective was to develop coatings that used the biocidal activity of copper, but with low negative impacts by reducing its leaching into the environment. This study reports the synthesis and characterisation of copper coordinating ligands, their formulation into coatings and testing of their antibacterial activity. A polyacylhydrazone and a series of simple acylhydrazones were synthesised and coordinated to Cu(II), but were considered unsuitable due to either their poor water-solubility or high levels of copper leaching. In an alternative approach, copper was successfully chelated to the tetraazamacrocycle, cyclen, and used to synthesise Cu(II)-cyclen functionalised silica particles, which were successfully combined with commercial paint formulations. These functionalised products showed poor antibacterial activity when incorporated into epoxy coatings, probably due to the low copper content of the formulations. However, these ligands may have other applications, such as removal of heavy metals from contaminated effluent steams.

In this review, we summarize recent work on the “green synthesis” of carbon nanoparticles (CNPs) and their application with a focus on biomedical applications. Recent developments in the green synthesis of carbon nanoparticles, from renewable precursors and their application for environmental, energy-storage and medicinal applications are discussed. CNPs, especially carbon nanotubes (CNTs), carbon quantum dots (CQDs) and graphene, have demonstrated utility as high-density energy storage media, environmental remediation materials and in biomedical applications. Conventional fabrication of CNPs can entail the use of toxic catalysts; therefore, we discuss low-toxicity manufacturing as well as sustainable and environmentally friendly methodology with a focus on utilizing readily available biomass as the precursor for generating CNPs.