Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver malignancy after hepatocellular carcinoma and is associated with poor prognosis, due to late-stage diagnosis and limited therapeutic options. Although surgical resection is the only potentially curative treatment, it is feasible in just 20-30% of patients, underscoring the urgent need for innovative therapies. This thesis explores a novel nanoparticle (NP)-based drug delivery system (DDS) designed to target the cancer-associated fibroblast (CAF)-rich tumor microenvironment of iCCA. The platform consists of NPs with a core-shell architecture, combining a polymeric core for efficient drug encapsulation with a lipid shell enabling surface functionalization. The DDS was engineered to deliver SR1078, a hydrophobic agonist of retinoic acid receptor-related orphan receptors α/γ, known to promote anti-tumor activity.