Nanoscale materials can be manipulated for a variety of uses in matters pertaining to nanomedicine, specifically in vivo targeting of materials. A novel norbornene-based analogue of a gadolinium-containing small molecule contrast agent (Gd-DOTA) was polymerized to form the hydrophilic component of water-soluble or amphiphilic block copolymers. We synthesized a small library of gadolinium-containing polymers using ring-opening metathesis polymerization. Different ratios of hydrophilic-to-hydrophobic block copolymers allowed access to spherical micellar nanoparticles or fibromicellar structures, with the gadolinium-containing block displayed as the shell of the particle. A hydrophilic polymer, completely dispersed in water, was synthesized in the same manner. Subsequent nanoparticle formulation following ROMP allowed us to synthesize chemically similar materials with dramatically different nanoscale morphologies: either dispersed polymers, micellar nanoparticles, or fibromicellar nanoparticles in an aqueous environment. The effects of morphology in vivo were studied via intraperitoneal injection of materials in to C57B1/6 mice. Real-time imaging of mice were performed using a 7T MRI instrument. T1 analysis of the bladder showed clearance of the small-molecule and polymeric materials within 2 hours. Nanoparticles, on the other hand, showed limited clearance via the bladder, while qualitative analysis showed considerable retention of these materials in the IP space several hours after injections. For all materials, complete clearance was observed after one week. Extended retention in the IP space and full clearance of nanomaterials one week post-IP injection has implications for treatment of peritoneal cancers.

Morphological dependence of biodistribution and clearance rates on MR-contrast agent labeled polymeric nanomaterials

248th National Meeting (2014)

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