An esterase-activated prodrug against pancreatic cancer by imaging-guided photodynamic immunotherapy

Photodynamic therapy (PDT) has received much attention as a promising modality for tumor treatment. However, the weak targeting ability of conventional photosensitisers and the metastasis of malignant tumors have severely limited the development of PDT. To address this, an esterase-activated prodrug (BPYM) has been developed for imaging-guided photodynamic therapy cascade immunotherapy for the treatment of pancreatic cancer. Upon reaction with esterase, BPYM releases the photosensitiser BPY and exhibits strong red fluorescence emission, which is further enhanced by the aggregation-induced emission (AIE) characteristics of BPY. Interestingly, the activation of the fluorescence signal simultaneously indicates the activation of photosensitivity capabilities. Under white light irradiation, activated BPYM can generate large amounts of reactive oxygen species (ROS) to induce apoptosis in pancreatic cancer cells. More importantly, BPYM-mediated PDT can trigger immunogenic cell death (ICD) and elicit a systemic anti-tumor immune response. Ultimately, this imaging-guided PDT not only precisely ablates the primary pancreatic cancer tumors, but also inhibits the growth of distant tumors through an immune response. In summary, we report a strategy to achieve photodynamic immunotherapy for the treatment of pancreatic cancer through the rational design of an esterase-activated prodrug.