Ovarian cancer is difficult to detect in the early stages, but a targeted, nanoparticle-based drug delivery system could make the treatment more effective even at advanced stages, and therefore the prognosis less deadly. Recent work has investigated various types of drug nanoparticles, but the polymer-based system proposed herein is unique in its incorporation of several problem-solving features. Ring opening metathesis polymerization (ROMP) is used to create covalent drug linkages, a pH-sensitive hydrophobic block allows release of the drug from the nanoparticle core in a controlled manner, and a high density of targeting peptides decorate the shell of the particle and direct it specifically toward, and accumulate in, diseased tissue. Covalent linkages allow for the drug to avoid immediate burst release upon administration, which leads to increased residence time in the body. A pH-sensitive core includes functionality which is protonated in the acidic intracellular compartments, causing the micellar arrangement to disassemble, allowing direct exposure of the hydrophobic drug. In addition, targeting peptides allow for preferential binding to overexpressed receptors of interest, permitting accumulation in the tumor space and leaving healthy cells and tissue intact when delivered via the intraperitoneal route. The combined aspects of this approach allow for an effective, stable platform which can deliver a chemotherapeutic agent specifically to the site of interest, sparing healthy tissue, thus ameliorating the severe side effects of cancer therapy.<br/>

Clinically-translatable, targeted, polymeric nanoparticles for tissue accumulation

253rd National Meeting (2017)

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