Development of ROS-Activated Dormant Photosensitizers with Theranostic Capabilities

ZHANG, WANG; MCCAIN, JULIA; COSA, GONZALO; SOL ROMINA MARTINEZ

Montreal

Congreso; 22nd Chemistry and Biochemistry Graduate Research Conference; 2019

Photodynamictherapy (PDT) is an established therapeutic technique for the treatment ofdiseases including cancer and bacterial infections. PDT employs photosensitizerswhich, upon photoexcitation, sensitize singlet oxygen (1O2),a cytotoxic reactive oxygen species (ROS). A risk of PDT is damage to surrounding healthy tissues when lightis applied. Activation of a dormant photosensitizer by reaction with a chemicalcue would mitigate undesired activity in healthy tissues. In 2016, our groupreported a dormant photosensitizer that activates upon scavenging ROS todeliver 1O2 specifically in cells under oxidative stressassociated with increased ROS generation, i.e. bacteria after treatment withantibiotics. The dormant photosensitizer combines a boron-dipyrromethene(BODIPY) photosensitizer with the antioxidant chromanol ring of α-tocopherol asa trap which quenches the excited photosensitizer via intramolecularphotoinduced electron transfer (PeT), preventing the sensitization of 1O2.ROS-mediated oxidation of the trap prevents quenching, activating the photosensitizer.Upon activation, our second-generation dormant photosensitizer sensitizes 1O2and also exhibits fluorescence. Thus, we may simultaneously monitor the levelof ROS using fluorescence microscopy and produce lethal 1O2under oxidative stress conditions. We aim to better understand ROS production inbacteria upon treatment with antibiotics and harness this oxidative stress to selectivelyinduce a PDT effect.