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, and 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; 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, which fully meet the stability requirements for injectable formulations in clinical applications; furthermore, the release rate of LL-PTP/ZnPc in tumor tissue was significantly higher (6.2-fold) than that in serum, which is significantly beneficial for the therapeutic effect of nanoparticles at the tumor site. To investigate the targeted uptake of LL-PTP/ZnPc, qualitative and quantitative analyses were performed using confocal laser scanning microscopy (CLSM) and flow cytometry, respectively, with the result that LL-PTP/ZnPc enhanced the uptake of nanoparticles by PANC-1 cells (a pancreatic cancer cell line) through Plectin-1-mediated endocytosis with an efficiency 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, with the finding 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, which effectively improved the effect of PDT on pancreatic cancer.