Abstract
Currently, effective therapeutic modalities for pancreatic ductal adenocarcinoma (PDAC) are quite limited, leading to gloomy prognosis and ∼6-months median patient survival. Recent advances showed the promise of photodynamic therapy (PDT) for PDAC patients. Next generation photosensitizers (PS) are based on "organelle-targeted-PDT" and provide new paradigm in the field of precision medicines to address the current challenge for treating PDAC. In this investigation, we have constructed a novel PS, named as N b B, for precise and simultaneous targeting of endoplasmic reticulum (ER) and lipid droplets (LDs) in PDAC, based on the fact that malignant PDAC cells are heavily relying on ER for hormone synthesis. Our live cell imaging and fluorescence recovery after photobleaching (FRAP) experiments revealed that N b B is quickly targeted to ER and subsequently to LDs and shows simultaneous dual fluorescence color due to polar and nonpolar milieu of ER and LDs. Interestingly, the same molecule generates triplet state and singlet oxygen efficiently and causes robust ER stress and cellular lipid peroxidation, leading to apoptosis in two different PDAC cells in the presence of light. Together, we present, for the first time, a potential next generation precision medicine for ER-LD organelle specific imaging and PDT of pancreatic cancer.