The use of nanomaterials in medical applications offers the promising possibility to deliver drugs through the selective accumulation of therapeutics in diseased tissue. In recent studies of the Gianneschi lab it has been demonstrated that enzyme-responsive micellar nanoparticles undergo a morphological transition from spherical-shaped materials into network-like assemblies when acted upon matrix metalloproteinases (MMPs). In xenograft mice this beneficial morphology switch leads to the accumulation and retention of these materials within tumor tissue in response to tumor-related overexpressed MMPs.<br/>We present an approach in which we utilize these enzyme-responsive nanoparticles and their enzymatically formed assemblies as a scaffold to deliver a large biomolecule such as a protein by the means of a bioorthogonal cycloaddition reaction. We have synthesized MMP-responsive peptide polymer amphiphiles by ring-opening metathesis polymerization (ROMP) followed by the conjugation of a strained alkene. After assembling these into micellar nanoparticles we successfully conjugated a tetrazine-labeled membrane protein. The cycloaddition reaction with the protein was still efficient after the aggregation of our material into network-like assemblies. We envision that the in-tumor agglomerated nanoparticles may be labeled <i>in vivo</i> with any therapeutic biomolecule and as such facilitate a localized therapy at the tumor site.

Enzyme-responsive nanoparticles for the targeted delivery of tetrazine-labeled proteins

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.