Tumor Microenvironment-Regulated and Reported Nanoparticles for Overcoming the Self-Confinement of Multiple Photodynamic Therapy.

The efficiency of photodynamic therapy (PDT) highly depends on the tumor oxygenation state. However, PDT itself can not only cause oxygen depletion but also prevent oxygen supply in tumors. Such self-confinement effect significantly limits the efficacy of PDT, especially fractionated PDT (fPDT). Herein, we proposed a multifunctional nanoparticle system having a four-pronged pipelined therapeutic scheme to address this issue. It performed oxygen supply and tumor microenvironment modulation together to effectively maintain tumor oxygenation even after multiple PDT fractions. It also introduced a new photosensitizer that not only was highly efficient in producing ROS but also could visually report tumor oxygenation state in a real-time fashion. All these functions were integrated into a single nanoparticulate system to obtain pipeline-style teamwork, which was then applied for the fPDT on a mice tumor model, and achieved significantly better tumor oxygenation even after multiple PDT fractions, ending up with a better tumor inhibition efficiency.