Seamlessly Crossing Biological Barriers with a Low Molecular Weight Photosensitizer to Cure Aggressive Tumours with Photodynamic Therapy

We present LUZ51, a new fluorinated bacteriochlorin of relatively low molecular weight (595 Da), which is a highly phototoxic agent but still with a favourable safety profile1. LUZ51 is an effective candidate for PDT, especially for tumors characterized by high desmoplasia. In vitro studies were conducted to evaluate uptake kinetics, phototoxicity and dark toxicity. The therapeutic effect of LUZ51-based PDT was evaluated in vivo in different models of cancer. LUZ51 is rapidly up-taken by cancer cells and has a phototoxicity in the low nanomolar region. In vivo, low-PDT regimen with LUZ51 significantly increases the overall survival of mice bearing tumors of moderate aggressiveness, such as subcutaneous CT26 tumors, as well as of highly aggressive tumors like 4T1 orthotopic tumors, which are characterized by desmoplasia and a high immunosuppressive environment.