Developing optical ratiometric nanosensors/nanoprobes for biomedical applications.

Abstract

This thesis presents the development of three ratiometric fluorescent PEBBLE (Photonic Explorers for Bioanalysis with Biologically Localized Embedding) nanosensors/nanoprobes: the PDMA (poly(decyl methacrylate))-based nanosensors for dissolved oxygen molecules, the ORMOSIL (organically modified silicate)-based oxygen nanosensors and the ORMOSIL-based singlet oxygen nanoprobes (the very first such ratiometric singlet oxygen nanoprobes ever developed). The PDMA oxygen nanosensors have been used for dissolved oxygen concentration measurements inside highly scattering biosamples such as human plasma. The ORMOSIL oxygen nanosensors have been successfully injected into live C6-glioma cancer cells via gene-gun delivery for real-time measurements of intracellular oxygen. Both PDMA and ORMOSIL oxygen nanosensors have demonstrated great improvements over previous oxygen PEBBLE nanosensors. The singlet oxygen nanoprobes have been utilized successfully to monitor the singlet oxygen production efficiency of dynamic nanoplatforms developed for photodynamic therapy of cancer. Furthermore, the introduction of ORMOSIL as a new PEBBLE matrix for both hydrophobic and hydrophilic dyes has significantly advanced the PEBBLE technology. This thesis also introduces a new ratiometric approach that makes the nanofabrication of PEBBLE nanosensors/nanoprobes more flexible, convenient and cheaper. The work presented indicates that these PEBBLE nanosensors/nanoprobes can be utilized in the near future for many other biomedical applications.