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

Area of Science:

• Biomedical Engineering
• Cancer Research
• Immunotherapy

Background:

• Photodynamic therapy (PDT) shows promise for tumor treatment but faces challenges with photosensitizer targeting and tumor metastasis.
• Developing effective strategies for pancreatic cancer treatment remains a critical medical need.

Purpose of the Study:

• To develop an esterase-activated prodrug (BPYM) for imaging-guided photodynamic therapy and cascade immunotherapy in pancreatic cancer.
• To enhance the targeting and therapeutic efficacy of PDT by integrating fluorescence imaging and immune response.

Main Methods:

• Design and synthesis of an esterase-activated prodrug (BPYM) that releases a photosensitizer (BPY) upon esterase activation.
• Utilizing aggregation-induced emission (AIE) characteristics of BPY for enhanced fluorescence imaging and photosensitivity.
• Investigating BPYM-mediated PDT-induced reactive oxygen species (ROS) generation, apoptosis, and immunogenic cell death (ICD) in pancreatic cancer cells.
• Evaluating the systemic anti-tumor immune response and inhibition of distant tumor growth.

Main Results:

• BPYM releases BPY, showing enhanced red fluorescence and photosensitivity upon esterase activation.
• Activated BPYM effectively generates ROS, inducing apoptosis in pancreatic cancer cells under white light irradiation.
• BPYM-mediated PDT triggers ICD and elicits a systemic anti-tumor immune response, leading to the ablation of primary tumors and inhibition of distant metastases.

Conclusions:

• The developed esterase-activated prodrug offers a promising strategy for imaging-guided photodynamic immunotherapy of pancreatic cancer.
• This approach overcomes limitations of conventional PDT by improving targeting and leveraging the immune system for comprehensive tumor control.