Reservoir-based devices for the monitoring and treatment of disease

Abstract

Cancer mortality still remains high despite significant investments in diagnostics, drug development, and treatment. The systemic route is convenient both for routine monitoring and for drug administration. Local cancer biomarker concentrations, however, are more indicative of the state of solid tumors and their response to therapy. Furthermore, local drug delivery can achieve efficacy where systemic treatments fail. This dissertation describes two reservoir-based devices to enable such local approaches. We are applying superparamagnetic crosslinked iron oxide nanoparticles (CLIO) for the quantitative measurements of soluble cancer biomarkers. These nanoparticles are functionalized to react specifically in the presence of their target analyte. An implanted device with a size-exclusion membrane was used to contain the CLIO and to expose them to the cancer milieu. The system was designed to be deployed deep within the body and indirectly detect cancer cells and their activity by their secreted products, which are produced at a very high copy number by each cell. A reservoir-based polymeric device has also been applied for local chemotherapy. A biodegradable polymer microchip was designed in our group to independently deliver more than one therapeutic agent. Only in vitro release of active compounds had been previously demonstrated. The work in this thesis achieves local drug therapy from the polymer microchip and demonstrates efficacy against an in vivo tumor model of brain cancer. The reservoir-based device approach has the potential to enable early detection of cancer recurrence, personalized drug treatments, and localized multi-drug therapy.