Nanomaterials are becoming increasingly useful in a number of applications in nanomedicine due to the unique properties they exhibit compared to their small molecule analogues. We utilize ring-opening metathesis polymerization to synthesize block copolymer amphiphiles that assemble in to discrete nanostructures. These block copolymers incorporated a poylmerizable analogue of the MRI contrast agent Gd-DOTA as a non-invasive imaging reporter. Polymers that contained the Gd-DOTA moiety as the hydrophilic component of the polymer amphiphile assembled in to spherical or fibrillar nanostructures, depending on the identity of the polymer. These materials were studied with respect to their contrast enhancing abilities using in vitro techniques such as NMRD, and in vivo using live animal imaging; the materials were observed to provide contrast both in vitro and in vivo. Responsive polymeric nanoparticles incorporating the Gd-DOTA moiety as an imaging reporter were also synthesized. Previous work in our lab has shown that enzyme-responsive polymeric nanomaterials labeled with fluorescent dyes accumulate in cancerous tumors following intravaneous injection. However, fluorescence imaging presents a multitude of issues, including background auto-fluorescence and clinical translatability. Polymers were synthesized incorporating an enzyme-responsive peptide in addition to the Gd-DOTA monomer. The enzyme-responsive peptide is a substrate for matrix metalloproteinases, enzymes overexpressed in cancerous tissue. After assembly of the nanoparticles in aqueous environment, the peptide brush is displayed at the water interface. Upon treatment with MMPs the peptide sequence is cleaved at the recognition site. This disrupts the amphiphilic nature of the polymer, which results in a morphology switch, or aggregation event. We aim to visualize this aggregation of these responsive materials at the site of interest, here, cancerous tissue, in real-time. If successful, this strategy could provide a new diagnostic or imaging platform.

Magnetic resonance imaging using responsive, targeted, shaped polymeric nanostructures

251st National Meeting (2016)

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