Student Presentation -- Ryan Robinson
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Ph.D. Dissertation Defense, Thursday July 27, 2017 -- Bioengineering as an Approach for Improved Disease Diagnosis and Treatment

SMBB 3250, 9:30 am

Speaker: Ryan Robinson. Advisor: Dr. Marc Porter


Abstract:

Tuberculosis (TB) is a treatable disease that kills nearly 2 million each year. However, accurate and sensitive low-cost diagnostic tests for TB are not available resource-poor areas where >95% of TB-related deaths occur. Antigenic based diagnostics offer promising strategies for meeting the TB detection needs, with the antigen mannose-capped lipoarabinomannan (ManLAM) giving excellent clinical specificity but varied clinical sensitivity. Complexation of ManLAM with serum components limit its detection, requiring pretreatment of serum to enable clinically relevant limits of detection in ELISA and SERS sandwich immunoassays. Digestion of serum proteins with Proteinase K and dithiothreitol at elevated temperatures improves ManLAM recovery and immunoassay-based clinical sensitivities, providing detection at picomolar concentrations. Automation of fluid handling was implemented to improve assay performance and reliability, and to investigate optimal microtiter plate washing techniques and parameters. Pretreatment and automation combined with our ELISA and SERS TB immunoassays should allow for an assessment of ManLAM as a TB marker.

Prostate cancer is also widespread, detectable, and potentially treatable, depending on the stage of cancer. Localize prostate cancer can be removed with surgery or alternative approaches, having high 15-year survivability rates (>96%), highlighting the importance of diagnostics and frequent testing. Advanced localized prostate cancer impacting surrounding tissues relies on less effective chemotherapeutics, radiotherapy, or combination approaches. However, if distant metastases form treatment options and survivability are low (29% after 5 years). Nanomedicine approaches could treat advanced localized prostate cancers, improving the prognosis for these patients. Plasmonic photothermal therapy (PPTT) administered with gold nanoconstructs could be used to overcome drug delivery difficulties by reducing uptake of the reticuloendothelial system, and minimizing side effects. Mild hyperthermic conditions increase macromolecular uptake, and PPTT can also be used for ablative cancer cell destruction. Particle shape, size, and surface chemistry greatly influence biodistribution, optical and heating properties, tumor uptake, macromolecular delivery enhancement, excretion rates, and cytotoxicity. These are each evaluated for gold nanorods and nanocages. The results show that nanocages may offer a better approach to PPTT, and may even allow for tumor specific drug delivery, removing the need for secondary polymer therapeutics.