Micro- and Nanostructured Optical Sensors for Doxorubicin Functionalized through Layer-by-Layer Assembly

This thesis focuses on the development of optical chemical sensors for biomedical applications, particularly for monitoring the anticancer drug Doxorubicin (DXR), widely used for treating various cancers but associated with serious side effects like cardiomyopathy. Real-time DXR monitoring through point-of-care or implantable sensors could enhance chemotherapy by improving drug dosage. The first type of DXR sensors uses coumarin-doped polystyrene microbeads acting as whispering gallery mode resonators. The particles were functionalized with polystyrene sulfonate (PSS) through the layer-by-layer technique. The WGM resonances showed a peak shift and broadening upon exposure to DXR, achieving a detection limit of 0.5 μg/mL in PBS. Selectivity and functionality in complex solutions were confirmed. The second sensor uses nanoporous silicon oxide (PSiOx) coated with fluorescent PSS-Rhodamine B (PSSRho). Owing to PSiOx's high surface area, the sensor exhibited stronger fluorescence than flat substrates. The presence of DXR induced a quenching of the PSS-Rhodamine B fluorescence proportionally to the drug concentration. Detection limits of 0.01 μg/mL in PBS and 0.05 μg/mL in ISF simulant were achieved in vitro; selectivity and biodegradability were also successfully verified. The fluorescence of implanted sensors was easily observable through the mice skin at different DXR concentrations.