NIR-Triggered "OFF/ON" Photodynamic Therapy through a Upper Critical Solution Temperature Block Copolymer

Activatable photodynamic therapy (A-PDT) has attracted great attention in precision medicine, which can be activated by endogenous or exogenous stimuli to selectively produce reactive oxygen species (ROS) at the disease site. Thermal responsive polymers with a lower critical solution temperature (LCST) have normally been utilized for constructing A-PDT system. Herein, we fabricated a photothermal activatable photosensitizer (A-PS) by the combination of thermal responsive porphyrin-containing P(AAm-co-AN-co-TPP)-b-POEGMA amphiphilic block copolymer with an upper critical solution temperature (UCST) of 42 °C and a cyanine dye of IR780. The photoactivity of porphyrin units could be severely inhibited by IR780 due to the fluorescence resonance energy transfer (FRET) from TPP to IR780 during blood circulation process ("OFF" state). After an uptake by A549 cells and then irradiated with 808 nm laser, A-PS nanoparticles were subsequently dissociated owing to the increased local temperature above the UCST of the polymer chains by excellent photothermal conversion of IR780, resulting in the enhanced photoactivity of TPP ("ON" state) and the remarkable antitumor effect. Therefore, the UCST-based A-PS extended the biological application of thermal responsive polymers, which may provide a new insight into the design of smart cancer therapeutic systems.