Stimuli-responsive Nanomaterials for Imaging and Delivery

We aim to develop novel materials that can respond to the unique biochemistry of disease, in particular microbial infection. This way, we take advantage of secreted enzymes and toxins to develop materials that can deliver conventional antimicrobials in a targeted way. For instance, in work recently developed by Ignacio Insua, we have been able to develop polyion complex particles that can selectively deliver an antimicrobial polymer in the presence of Pseudomonas aeruginosa.

Normalised antimicrobial activity over time of enzyme-responsive nanoparticles prepared at a 1:0.3 N:COOH ratio. Activity has been normalised by dividing the relative antimicrobial activity from PIC nanoparticles by that of the antimicrobial polymer. *** p < 0.001 between PAO1V and ΔlasAB (CI = 99.9%) after 4 hours. n = 3. From I. Insua et al., Enzyme-responsive polyion complex (PIC) nanoparticles for the targeted delivery of antimicrobial polymers. Polym. Chem. 7, 2684–2690 (2016).- Published by The Royal Society of Chemistry.

The system takes advantage of one of the limitations of antimicrobial polymers (i.e. their toxicity associated with their positive charge) to build the particles, by coacervation with a negatively charged peptide. This peptide includes a short enzyme-responsive sequence that can be selectively cleaved by P. aeruginosa elastase, one of the virulence factors produce by this pathogen at the site of infection. More importantly, neither the peptides nor the particles are degraded by human leucocyte elastase, produce by our immune system to fight infection/inflammation. As such, this system is fully selective and only delivers the antimicrobial if the elastase is present.  To the best of our knowledge this is the first time a system such as this has been developed for the delivery of last resort antimicrobials and can be a valuable tool in the fight against antimicrobial resistance. You can read the full paper here.