Synthesis, Characterization and Application of Targeted Nanocarrier Improving Photodynamic Therapy for Pancreatic Cancer

LL-PTP, a pancreatic cancer-targeted nanocarrier, was synthesized via click chemistry. Subsequently, the insoluble photosensitive drug zinc phthalocyanine (ZnPc) was physically encapsulated within LL-PTP to fabricate LL-PTP/ZnPc nanoparticles. The critical aggregation concentration (CAC) of LL-PTP was determined to be 52.97 μg/mL. The LL-PTP/ZnPc nanoparticles, formed by the physical encapsulation of ZnPc, appeared as a blue transparent solution. Characterizations revealed that the ZnPc loading efficiency of these nanoparticles was 20.1 ± 1.4%, with a hydrated particle size of 89.18 ± 0.21 nm. Notably, the nanoparticles exhibited excellent storage stability and serum stability, fully meeting the stability requirements for injectable formulations in clinical applications. Furthermore, the release rate of LL-PTP/ZnPc in tumor tissue was found to be over 6-fold higher than that in serum—a property that significantly favors the therapeutic efficacy of the nanoparticles at the tumor site. To investigate the targeted uptake behavior of LL-PTP/ZnPc, qualitative and quantitative analyses were performed using confocal laser scanning microscopy (CLSM) and flow cytometry, respectively. The results demonstrated that LL-PTP/ZnPc enhanced the uptake of nanoparticles by PANC-1 cells (a pancreatic cancer cell line) through Plectin-1-mediated endocytosis. This uptake efficiency was significantly superior to that of LL/ZnPc (non-targeted control nanoparticles) and free ZnPc. Intracellular reactive oxygen species (ROS) levels were detected using the DCFH-DA probe. It was observed that LL-PTP/ZnPc, upon light irradiation, induced a marked increase in intracellular ROS production—an effect that is conducive to achieving enhanced photodynamic therapy (PDT) efficacy against pancreatic cancer. In conclusion, this study successfully developed LL-PTP, a targeted nanocarrier for pancreatic cancer, and achieved efficient loading of ZnPc. The resulting LL-PTP/ZnPc nanoparticles effectively improved the PDT effect against pancreatic cancer, highlighting their potential as a promising therapeutic platform for this malignancy.