Nanotechnology-Driven Strategies to Enhance Immunotherapy in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal cancers, characterized by a dense stromal microenvironment and resistance to conventional therapies. Recent advancements in nanotechnology offer promising strategies to improve the efficacy of therapeutic interventions by targeting specific components of the tumor microenvironment (TME). This thesis investigates the potential of nanotechnology-based approaches to remodel the TME and enhance immunotherapy outcomes in PDAC. In the first study the utilization of hollow Cu₂MoS₄ nanoparticles is examined to ascertain whether this approach can facilitate enhanced penetration of the tumor and augment the immune response. The second study evaluates the efficacy of Midkine nanobody-engineered semiconducting polymer nanoparticles (D4 Nb-PCP NPs) in inducing immunogenic cell death (ICD) and improving photodynamic therapy (PDT) outcomes in PDAC. Finally, the third study focuses on an innovative gemcitabine-based polymeric nanocarrier (PGEM) that activates the cGAS-STING pathway, reshaping the tumor immune microenvironment and improving the response to immunotherapy. The combined results of these studies offer insights into innovative nanotechnology-based solutions for addressing the therapeutic resistance of PDAC and enhancing the efficacy of immunotherapeutic strategies.