6533b7d1fe1ef96bd125d666

RESEARCH PRODUCT

Dual Enzyme-Responsive Capsules of Hyaluronic Acid-block-Poly(Lactic Acid) for Sensing Bacterial Enzymes.

Holger SchönherrRonald E. UngerKatrin-stephanie TückingVerena Grützner

subject

Fluorescence-lifetime imaging microscopyStaphylococcus aureusMaterials sciencePolymers and PlasticsCell SurvivalPolymersDrug CompoundingPolyestersMolecular Sequence DataPrimary Cell CultureHyaluronoglucosaminidaseBiosensing TechniquesFluorescence spectroscopyNanocapsuleschemistry.chemical_compoundDynamic light scatteringBacterial ProteinsNanocapsulesHyaluronidaseAmphiphileMaterials ChemistrymedicineHumansLactic AcidHyaluronic AcidMicellesFluorescent DyesCycloaddition ReactionRhodaminesOrganic Chemistrytechnology industry and agricultureEndothelial CellsDermisLactic acidchemistryBiochemistryCarbohydrate SequencePseudomonas aeruginosaBiophysicsLiberationEndopeptidase Kmedicine.drug

description

The synthesis of novel amphiphilic hyaluronic acid (HYA) and poly(lactic acid) (PLA) block copolymers is reported as the key element of a strategy to detect the presence of pathogenic bacterial enzymes. In addition to the formation of defined HYA-block-PLA assemblies, the encapsulation of fluorescent reporter dyes and the selective enzymatic degradation of the capsules by hyaluronidase and proteinase K are studied. The synthesis of the dual enzyme-responsive HYA-b-PLA is carried out by copper-catalyzed Huisgen 1,3-dipolar cycloaddition. The resulting copolymers are assembled in water to form vesicular structures, which are characterized by scanning electron microscopy, transmission electron microscopy, dynamic light scattering (DLS), and fluorescence lifetime imaging microscopy (FLIM). DLS measurements show that both enzymes cause a rapid decrease in the hydrodynamic diameter of the nanocapsules. Fluorescence spectroscopy data confirm the liberation of encapsulated dye, which indicates the disintegration of the capsules and validates the concept of enzymatically triggered payload release. Finally, cytotoxicity assays confirm that the HYA-b-PLA nanocapsules are biocompatible with primary human dermal microvascular endothelial cells.

10.1002/marc.201500076https://pubmed.ncbi.nlm.nih.gov/25940300