Overcoming Hypoxia and Light Penetration Limitations in Photodynamic Therapy

Photodynamic therapy (PDT) has been developed as a next generation, minimally invasive cancer treatment. However, it remains highly challenging to generate reactive oxygen species (ROS, including 1O2, O2·, OH·, and H2O2) in hypoxic tumor environments and to efficiently deliver light into deeply located tumor tissue. To address these issues, our group develop ambiphilic photocatalyst, called BTP, which targets endomembrane and generate hydroxy radical through photooxidation of water. The released the strongest oxidizing ROS, OH· can oxidize membrane, activating Gasdermin-D and inducing pyroptic cell death in pancreatic cancer cells while also stimulating immune activation. Next, to ensure efficient light delivery, we introduce three-dimensional, self-adaptative, implantable photonic device (IPD) providing tumor-specific and continuous light irradiation for maximal PDT efficacy. The IPD seamlessly adhered to the surface of orthotopic pancreatic ductal adenocarcinoma tumors. In active mouse models, long-term IPD therapy significantly reduced desmoplastic tumor volume without causing cytotoxicity in healthy tissue.