胰腺癌靶向纳米载体的合成、表征及其改善光动力治疗研究OA

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 u ptake 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.