Enzyme Degradable Polymersomes from Hyaluronic Acid-block-poly(ε-caprolactone) Copolymers for the Detection of Enzymes of Pathogenic Bacteria

We introduce a new hyaluronidase-responsive amphiphilic block copolymer system, based on hyaluronic acid (HYA) and polycaprolactone (PCL), that can be assembled into polymersomes by an inversed solvent shift method. By exploiting the triggered release of encapsulated dye molecules, these HYA-block-PCL polymersomes lend themselves as an autonomous sensing system for the detection of the presence of hyaluronidase, which is produced among others by the pathogenic bacterium Staphylococcus aureus. The synthesis of the enzyme-responsive HYA-block-PCL block copolymers was carried out by copper-catalyzed Huisgen 1,3-dipolar cycloaddition of omega-azide-terminated PCL and omega-alkyne-functionalized HYA. The structure of the HYA-block-PCL assemblies and their enzyme-triggered degradation and concomitant cargo release were investigated by dynamic light scattering, fluorescence spectroscopy, confocal laser-scanning microscopy, scanning and transmission electron, and atomic force microscopy. As shown, a wide range of reporter dye molecules as well as antimicrobials can be encapsulated into the vesicles during formation and are released upon the addition of hyaluronidase.