Tailoring Gold Nanoisland-Based Biosensors for Ultrasensitive Detection of Doxorubicin in Biological Fluids

Recent advancements in medical science have ushered in the era of “Personalized Medicine,” which tailors treatments to individual genetics, lifestyle, and environmental factors. A cornerstone of this approach is continuous monitoring and adjustment of treatment regimens to optimize effectiveness while minimizing side effects. In therapeutic drug monitoring (TDM), crucial for drugs like doxorubicin (DOX) with severe side effects, traditional methods such as spectrofluorimetry and chromatography are utilized, but they suffer from cost and complexity issues. Biosensors, especially those leveraging Localized Surface Plasmon Resonance (LSPR) and surface-enhanced Raman spectroscopy (SERS), offer a promising alternative. This study focuses on developing a cost-effective plasmonic biosensor using gold nanoislands semiembedded in a glass substrate. The LSPR platform, based on gold nanoislands (Au NIs) with an average diameter of 23 nm, offers a rapid method for ultrasensitive, label-free detection of DOX in biological fluids up to the nanomolar range, even in diluted (1:10) and undiluted blood serum samples from cancer patients receiving the drug. The method capitalizes on the extraordinary adhesion between the nanoislands and the glass matrix, preserving plasmon integrity while enhancing the electric field surrounding the nanoislands for improved sensitivity. Moreover, by exploiting nanoislands with Au/Al 2 O 3 core/shell structures with an average diameter and gap of about 70 and 7 nm, respectively, highly efficient SERS-active platforms are created, enabling the detection of ultralow DOX concentrations down to picomolar range, where the LSPR system is insensitive. The combined use of both systems enables the detection of DOX across a broad range, from low to high nanomolar concentrations, in biological fluids. This integration of semiembedded nanoislands presents a scalable and multifunctional approach suitable for point-of-care diagnostics, offering reproducible and stable characteristics over time.