| This thesis summarizes several developments in the use of ring-opening metathesis polymerization (ROMP) to construct drug-loaded polymer nanoparticles (PNPs). Utilizing doxorubicin-conjugated norbornene as the hydrophobic drug-containing component, ROMP-based amphiphilic block copolymers were prepared in high yields with good control over drug density, molecular weight, and size distribution. These co-polymers were assembled into narrowly disperse core-shell-type polymer nanoparticles that can release doxorubicin under mildly acidic conditions.;The efficacy of doxorubicin-containing PNPs (Dox-PNPs) were evaluated in vitro against neuroblastoma cell lines, demonstrated prolonged inhibition of tumor cell growth that was consistent with a slow release profile. Injection of Dox-PNPs into nude mice bearing breast cancer also showed inhibition of tumor growth more effectively than the free drug at 2.5 times the concentration and with minimized side effects.;Incorporation of targeting groups onto Dox-PNPs was accomplished utilizing synthetic handles on the surface of the particles, installed via modification of the hydrophilic poly(ethylene glycol) conjugated nobornene with easily displaceable sulfonyl esters. Post-nanoparticle-formation modification was used to graft HER2 antibodies that are overexpressed in several breast cancer cell lines onto the PNP surface. In vitro testing of HER2-modified Dox-PNPs showed them to be 20 times more specific toward HER2-over-expressing cells lines than unmodified PNPs.;Diagnostic capability by way of Gd-based magnetic resonance imaging (MRI) contrast agent was imparted onto indomethacin-containing PNPs via the copolymerization of gadolinium-conjugated ROMP monomers. The length of the gadolinium-containing block in the amphiphilic copolymer can be varied, resulting in several folds increase in the per-Gd relaxivity in the resultant particles. |
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