Presentation Type
Oral Presentation
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Background: Pancreatic ductal adenocarcinomas, originating from the epithelial cell lining of ducts, account for approximately 95% of tumors in this category, showcasing a survival rate of less than 5-7%. Unfortunately, little progress has been seen in the outcomes of patients with PDAC as tumor develops high desmoplasia and chemo-resistance to chemotherapeutic drugs, such as gemcitabine (Gem). The therapies are unable to penetrate to the fibrotic tumors leading to insufficient availability of the therapeutic drugs at the tumor site. We and others have shown that MUC13 is aberrantly expressed in pancreatic tumors but not in normal pancreas, which makes MUC13 as an excellent protein for specifically targeting pancreatic tumors. Herein, we demonstrate a unique ability of our in-house generated mouse and humanized monoclonal antibody of MUC13 to penetrate and target pancreatic cancer.
Methods: These antibodies have been conjugated with our recently developed novel patented superparamagnetic iron oxide nanoparticles (SPIONS) to deliver therapeutics specifically to pancreatic tumors. In this study, we are using curcumin that depletes tumor microenvironment and gemcitabine to investigate the efficacy of the MUC13 conjugated SPION in delivery of therapeutic drugs.
Results: Our results demonstrate that enhanced uptake of MUC13-SPION formulation in MUC13 positive (MUC13+) PanCa cells, compared with MUC13 null (MUC13-) cells as demonstrated by immunofluorescence, Prussian blue staining and flow cytometry experiments. Interestingly, the formulation resulted in sustained delivery of curcumin (CUR), enhanced inhibition of cell proliferation, migration and invasion in MUC13+ cells as compared with MUC13- cells, which suggests the targeting efficacy of the formulation. In PanCa orthotopic mice model, MUC13- SPION efficiently targeted pancreatic tumors resulting in significant tumor accumulation. We observed inhibition of tumor volume, metastasis, gem resistance and improved survival in mice treated with the formulation. Additionally, the tumor tissues from treated mice showed extensive downregulation of PCNA and expression of key proteins in SHH pathway, such as SHH, Gli-1, Gli-2, Patched 1, SMO, which has been associated with cancer progression and drug resistance.
Conclusion: In conclusion, the results indicate high therapeutic significance of MUC13-SPIONS for achieving pancreatic tumor specific delivery of drugs.
Academic/Professional Position
Faculty
Mentor/PI Department
Immunology and Microbiology
Recommended Citation
Dan, Nirnoy; Setua, Saini; Yallapu, Murali; Behrman, Stephen; Chauhan, Subhash; and Khan, Sheema, "Antibody mediated Targeted Drug Delivery approach for Pancreatic Tumors" (2024). Research Symposium. 3.
https://scholarworks.utrgv.edu/somrs/2024/talks/3
Included in
Antibody mediated Targeted Drug Delivery approach for Pancreatic Tumors
Background: Pancreatic ductal adenocarcinomas, originating from the epithelial cell lining of ducts, account for approximately 95% of tumors in this category, showcasing a survival rate of less than 5-7%. Unfortunately, little progress has been seen in the outcomes of patients with PDAC as tumor develops high desmoplasia and chemo-resistance to chemotherapeutic drugs, such as gemcitabine (Gem). The therapies are unable to penetrate to the fibrotic tumors leading to insufficient availability of the therapeutic drugs at the tumor site. We and others have shown that MUC13 is aberrantly expressed in pancreatic tumors but not in normal pancreas, which makes MUC13 as an excellent protein for specifically targeting pancreatic tumors. Herein, we demonstrate a unique ability of our in-house generated mouse and humanized monoclonal antibody of MUC13 to penetrate and target pancreatic cancer.
Methods: These antibodies have been conjugated with our recently developed novel patented superparamagnetic iron oxide nanoparticles (SPIONS) to deliver therapeutics specifically to pancreatic tumors. In this study, we are using curcumin that depletes tumor microenvironment and gemcitabine to investigate the efficacy of the MUC13 conjugated SPION in delivery of therapeutic drugs.
Results: Our results demonstrate that enhanced uptake of MUC13-SPION formulation in MUC13 positive (MUC13+) PanCa cells, compared with MUC13 null (MUC13-) cells as demonstrated by immunofluorescence, Prussian blue staining and flow cytometry experiments. Interestingly, the formulation resulted in sustained delivery of curcumin (CUR), enhanced inhibition of cell proliferation, migration and invasion in MUC13+ cells as compared with MUC13- cells, which suggests the targeting efficacy of the formulation. In PanCa orthotopic mice model, MUC13- SPION efficiently targeted pancreatic tumors resulting in significant tumor accumulation. We observed inhibition of tumor volume, metastasis, gem resistance and improved survival in mice treated with the formulation. Additionally, the tumor tissues from treated mice showed extensive downregulation of PCNA and expression of key proteins in SHH pathway, such as SHH, Gli-1, Gli-2, Patched 1, SMO, which has been associated with cancer progression and drug resistance.
Conclusion: In conclusion, the results indicate high therapeutic significance of MUC13-SPIONS for achieving pancreatic tumor specific delivery of drugs.