Lipid-based Codelivery of Doxorubicin and siRNA PD -L1, as a Multi-function Chemo - immunotherapy, Selective to PDAC via its MUC1 Overexpression

Overview

Pancreatic cancer is the second leading cause of death, with 90% of occurrences as Pancreatic ductal adenocarcinoma (PDAC). Doxorubicin (DOX) is the leading treatment for cancers, functioning by blocking topoisomerase II, an enzyme essential for cancer cel l division. However, chemotherapy penetration in PDAC is limited due to its dense stromal barrier and destructive tumor-microenvironment (TME). Herein, a pancreas -specific chemoimmunotherapy utilizing DOX, siRNA PD-L1, and MUC1 antibodies was designed for PDAC treatment. To begin, mPEG- b-PHEP were fabricated as the nanoparticle (NP) interior, exhibiting flow -core capability. These were loaded with DOX, which were later coated with an SiO2 layer for stability. Chitosan was then added as a binder for the inclusion of siRNA -PD-L1, to inhibit the PD -L1 pathway, restoring immune activity. Finally, DOPE-Anti-MUC1 was conjugated to the NP-surface, to provide friendly delivery through the TME, wit h selectivity to the overexpression of PDAC cell -surface MUC1. DOX-siRNA-DOPE dissolution studies in normal extracellular fluid (pH 7.4) versus that of the PDAC-TME (pH 6.8) demonstrate 100% degradation of the DOPE outer layer within five minutes. HPLC analysis was used to subsequently demonstrate DOX-siRNA release, where 95% of a 20ug DOX-load was released within the same 5 -minute period following introduction to a simulated PDAC-TME. To simulate DOX -siRNA-DOPE selectivity and function, an MUC1 ELISA -kit was modified using ATR -FTIR analysis, which highlighted adhesion of the NP’s DOPE-Anti-MUC1 functionality to PDAC -MUC-1 overexpression. Finally, Giant Unilamellar Vesicles (GUVs) were created with fluorescently -labeled lipid -bilayers that mimic both normal and PDAC cells (with MUC1). DOX-siRNA-DOPE again targeted PDAC GUVs due to Anti-MUC1 selectivity. DoDEA Europe

Competition history

• JSHS 2025 Category not listed

Resources

• National JSHS abstract book ↗

Related projects

Closest projects by meaning, across every fair and year in the corpus.