PEG conjugated BODIPY-Br₂ as macro-photosensitizer for efficient imaging-guided photodynamic therapy

Drug-free biocompatible nanoparticles with photosensitizers as both diagnostic and therapy agents represent an emerging approach for imaging-guided photodynamic therapy (PDT). Here, a NSH-active boron-dipyrromethene (BODIPY) derivative with a bromine substituted (BODIPY-Br₂, for simplicity, BDP-Br) photosensitizer was synthesized; it showed a high ability of generating reactive oxygen species (ROS) upon irradiation for PDT and near infrared fluorescence imaging ability. Then, a simple PEGylated BDP-Br (PEG-BDP) as a kind of macro photosensitizer was prepared which showed superior cellular uptake ability, high efficiency of imaging, and curing with PDT therapy in vitro and in vivo. After administration with a 4T1 orthotopic tumor model, the resultant PEG-BDP showed prolonged blood circulation and preferential tumor accumulation compared with free BDP-Br molecules. Once accumulated in tumor tissues, therapeutic effects of PEG-BDP could significantly suppress primary tumor growth and has no evident side effects at a weak irradiation energy as low as 35 mW cm^-2 for 20 minutes. The designation of this simple structure macro photosensitizer agent provides new avenues for efficient imaging-guided cancer PDT.