Pancreatic tumor immunosurveillance by curcumin superparamagnetic iron oxide nanoparticles 4299

Abstract Description We have shown that MUC13, a transmembrane mucin, is aberrantly expressed in pancreatic tumors, which makes MUC13 an excellent molecular target for targeting pancreatic tumors. Herein, we demonstrate unique ability of MUC13 antibody conjugated curcumin loaded superparamagnetic iron oxide nanoparticles (MUC13-CUR-SPION) to penetrate pancreatic tumors and effectively modulate pancreatic tumor immune surveillance. Our results demonstrate enhanced uptake of MUC13-SPION formulation in MUC13 positive (MUC13+) PanCa. Interestingly, the formulation resulted in sustained delivery of curcumin (CUR), inhibition of cell proliferation, migration and invasion in PanCa cells. In PanCa orthotopic mice model, MUC13-SPION efficiently targeted pancreatic tumors and observed marked inhibition of tumor growth. Additionally, the tumor tissues from treated mice showed extensive influence on tumor microenvironment including downregulation of PCNA and expression of key proteins in SHH pathway, such as SHH, Gli-1, Gli-2, Patched 1, and SMO. Moreover, the treatment increased T-cell infiltration and decreased immunosuppressive cells (T-reg and M-MDSC) in tumors that enhanced immune checkpoint immunotherapy (PD1/PD-L1, CTLA-4) response and drug resistance. In conclusion, the results indicate high therapeutic significance of MUC13-SPIONS for achieving pancreatic tumor specific delivery of drugs, modulation of pancreatic tumor immune surveillance and improving immunotherapy response. Funding Sources National Institutes of Health grants R01CA206069, R01CA210192 and R01CA204552. CPRIT TREC Award RP230419 and Integrated Cancer Research Core (ICRC)-RP210180. Herb Kosten foundation for pancreatic cancer research. NIH/NIMHD/U54 MD19970 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)