Thrombin-sensitive dual fluorescence imaging and therapeutic agent for detection and treatment of synovial inflammation in murine rheumatoid arthritis

Oxygen and indocyanine green loaded phase-transition nanoparticle-mediated photo-sonodynamic cytotoxic effects on rheumatoid arthritis fibroblast-like synoviocytes

“…7 It has been proposed and experimentally studied as a new RA synovectomy modality in the last few years. [8][9][10] However, limited penetrating ability of light is one of the reasons hampering further study of PDT-mediated therapeutic effect on RA. Compared with the light used in PDT, ultrasound has better penetrability, which can easily act on the lesion at a deep site.…”

Advanced Photosensitizer Activation Strategies for Smarter Photodynamic Therapy Beacons

“…Thrombin and urokinase‐type plasminogen activator are newly targeted proteases for PDT beacons . Figure highlights work by Busso et al., who developed a thrombin‐activated beacon for theranostic application in rheumatoid arthritis (RA), showing 10‐fold activation of pheophorbide a fluorescence and dose‐dependent PDT . While PDT has been previously explored in RA, this construct demonstrated selective activation and subsequent PDT effects localized only to the inflammatory lesions in arthritic joints, reaffirming the added layer of healthy, tissue‐sparing selectivity sought after with PDT beacons.…”

“…Though research has shown that PS modulation can be triggered by a number of biomarkers, certain targets stand out. Protease‐triggered PDT beacons have found a comfortable niche targeting cancer‐associated proteases such as MMPs, but new research continues to expand their application to new disease states using existing or new extracellular proteases. The future for these PDT beacons is likely to follow behind the steps of activatable fluorescence probes.…”

Fishing for fire: strategies for biological targeting and criteria for material design in anti‐inflammatory therapies

“…Starting from the observation that thrombin is overexpressed by activated synoviocytes in RA models, the group of Lange has been able to modulate the action of porphyrin‐based sensitizers in photodynamic therapy using a thrombin‐cleavable space. The sensitizers were covalently bound to a poly(lysine) backbone, and their crowding substantially inactivated them; upon cleavage, they regained their singlet oxygen photogenerating ability and were successfully employed for RA treatment and imaging with systemic parenteral administration . Finally, PLA2‐sensitive and phospholipid‐bound prodrugs have been developed in a liposomal form, for example, to release cytotoxic retinoid acid or the anti‐inflammatory/anti‐angiogenic fumagillin, which was able to significant improve RA in mice.…”