Year: 2019
Type: dissertation
Abstract: Despite the substantial burden imposed by osteoarthritis (OA) upon patients and healthcare systems across the world, there are still no effective disease-modifying treatments. A recent shift to view OA as a “whole joint disease” has generated opportunities for therapeutic innovations. Photodynamic therapy (PDT), a clinically approved and minimally invasive treatment modality, holds great potential for application in OA. Herein, we describe the development of a porphyrin molecular beacon, PPMMP13B, as a new approach to OA. Upon target protease-triggered activation, PPMMP13B demonstrates a near 12-fold increase in porphyrin fluorescence as well as the restoration of PDT capabilities through generation of reactive singlet oxygen. Selective activation in vitro occurs only in the presence of human-derived OA synovial fibroblasts. Additionally, a unique intra-articular biodistribution of this porphyrin construct is observed. These results provide the foundation for future studies investigating the therapeutic efficacy of porphyrin molecular beacons to treat OA.
Source: TSpace (University of Toronto)
Author: Connor Walsh
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3139679987