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Nanoparticles with switchable shells for virus sensing and inhibition

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Gold nanoparticles deliver greater diagnostic sensitivity

Nature-mimicking nanoparticles could revolutionise medical diagnostics and open the door to the next generation of antiviral drugs.

Health

Self-assembled monolayers (SAMs) – layers of organic molecules that assemble spontaneously on surfaces – are an important element of modern nanotechnology. Potential applications include the fabrication of extremely thin insulator films and nanoscale electronic devices. “Reversible self-assembled monolayers (rSAMs) are able to reversibly assemble on charged surfaces, to form molecularly defined layers,” notes rSAMs-NANO project coordinator Börje Sellergren, professor of Biomedical Technology at Malmö University, Sweden. “This behaviour gives them some potentially interesting biomimetic properties.” In particular, Sellergren and Marie Skłodowska-Curie research fellow, Yulia Sergeeva, were interested in whether rSAMs could be applied to mimic the way cells interact with their surroundings or their encounters with pathogens. This could be very useful in the fields of tissue engineering and biosensing, and eventually in developing ways of inhibiting virus-host cell interactions. “The key potential benefits we identified in using rSAMs were robustness, ease of manufacturing and short lead times combined with low cost,” says Sellergren. “For instance, virus antigen-based tests today currently rely on expensive and often difficult to produce antibodies. Overcoming these hurdles could speed up pandemic response actions and increase global testing availability.”

Sensitive diagnostic techniques

So the rSAMs-NANO project set about examining whether the application of rSAMs could improve on existing medical diagnostic and therapeutic techniques. “This research was inspired by previously published work on nanoparticle-based pathogen inhibitors,” explains Sellergren. “For instance, glycan decorated gold nanoparticles were shown to have promising inhibitory properties on bacteria and virus particles.” These nanoparticles lacked the dynamic, biomimetic features of rSAMs. To test their hypothesis, the project team deposited rSAMs as adaptable shells on gold core nanoparticles, to see if greater diagnostic sensitivity could be achieved. “We systematically investigated the influence of gold nanoparticle size, anchor layer properties and rSAM composition on the stability of the core-shell particles,” adds Sellergren. “We were able to identify a unique combination that allowed us to achieve stability.” The efficiency of these dynamic shell nanoparticles in detecting infection was trialled using capsid proteins and inactive virus particles. Nanoparticle sensors for example were validated against different influenza virus strains. In these experiments, the project discovered that the ligand modified nanoparticles interacted strongly with their receptors. “Furthermore, ligand mobility significantly strengthened target binding. This in turn led to detection sensitivities that exceeded those seen with alternative receptors such as antibodies. “Ultimately, we were able to show that we could produce stable, gold-core rSAM-shell nanoparticles,” says Sellergren. “These were then shown to interact strongly with their receptors.”

Biosensing breakthrough

These findings could represent a significant breakthrough in biomimetic biosensing and diagnostic techniques. The materials pioneered in the project have been patented by the inventors and are being exploited by a small start-up company established following project completion. Licence agreements are currently being negotiated. The techniques pioneered through the rSAMs-NANO project could conceptually also be used to inhibit virus entry by blocking the receptor at the early stages of infection. This could be of interest to the pharmaceutical sector, with a view to eventually developing next-generation antiviral drugs. “With this Marie Skłodowska-Curie Actions programme project, we also sought to support a researcher with exceptional skills in this field,” notes Sellergren. “These skills matched perfectly with what we required in order to progress towards our goals.”

Keywords

rSAMs-NANO, nanotechnology, SAMs, biomimetic, virus, cell, gold, nanoparticles

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