Abstract:

Objective The aim of this study was to explore the therapeutic effect and potential mechanism of targeting photodynamic therapy using calcium carbonate nanoparticles in pancreatic cancer. Methods Ce6@Ca⁃ CO3 were prepared by gas diffusion method to load Ce6，and then modified with polyethylene glycol. Linsitinib was used to target insulin⁃like growth factor 1 receptor（IGF⁃1R）to prepare CLCP nanoparticles with acid⁃responsive and active targeting abilities. The characterization of CLCP was investigated. The active targeting ability and the therapeutic effect of CLCP were evaluated in vitro and in vivo. Results The average hydrated size of CLCP was （121.5 ± 5.2）nm with spherical shape under the electron microscope. The loading efficiency of Ce6 was 63.2% and the loading content was 16.37%. CLCP degraded rapidly in a weak acidic（pH = 6.5）environment. Pancreatic cancer cells have increased uptake of CLCP（P < 0.001）. CLCP⁃mediated photodynamic therapy decreased cell viability（P < 0.01）by inducing wider cells death compared with untargeted group（P < 0.001）. CLCP⁃mediated photodynamic therapy effectively prolonged the survival period of mice and pathologically caused cancer cells apoptosis increased. Besides，CLCP ⁃mediated photodynamic therapy enhanced the recruitment of CD8 + T cells in tumors. Conclusion We successfully synthesized the targeting CLCP based on IGF⁃1R to efficiently deliver Ce6， and CLCP⁃mediated photodynamic therapy has satisfactory therapeutic effect due to the direct killing of cancer cells and the activation of anti⁃tumor immune，which provides a novel strategy for pancreatic cancer treatment. 

Key words:

pancreatic cancer, calcium carbonate, nanoparticles, photodynamic therapy