HighlightsCurrent clinical studies of photodynamic therapy against pancreatic cancer are reviewed.Advantages of nanoparticles in boosting therapeutic efficacy of photodynamic therapy for pancreatic cancer treatment are summarized.Challenges and outlook for the future development of nanoparticles-based photodynamic therapy in human are discussed. AbstractPatients with pancreatic cancer (PCa) have a poor prognosis apart from the few suitable for surgery. Photodynamic therapy (PDT) is a minimally invasive treatment modality whose efficacy and safety in treating unresectable localized PCa have been corroborated in clinic. Yet, it suffers from certain limitations during clinical exploitation, including insufficient photosensitizers (PSs) delivery, tumor-oxygenation dependency, and treatment escape of aggressive tumors. To overcome these obstacles, an increasing number of researchers are currently on a quest to develop photosensitizer nanoparticles (NPs) by the use of a variety of nanocarrier systems to improve cellular uptake and biodistribution of photosensitizers. Encapsulation of PSs with NPs endows them significantly higher accumulation within PCa tumors due to the increased solubility and stability in blood circulation. A number of approaches have been explored to produce NPs co-delivering multi-agents affording PDT-based synergistic therapies for improved response rates and durability of response after treatment. This review provides an overview of available data regarding the design, methodology, and oncological outcome of the innovative NPs-based PDT of PCa.