Preliminary Development and Evaluation of Folic Acid-Targeted Superparamagnetic Albumin Nanoparticles for MicroRNA Delivery and Magnetic Resonance Imaging in Cholangiocarcinoma

Background: Cholangiocarcinoma (CCA) is an aggressive malignancy with poor prognosis, underscoring the need for novel diagnostic and therapeutic strategies. MicroRNAs (miRNAs) hold therapeutic promise but face delivery challenges. This study aimed to develop folic acid (FA)-targeted superparamagnetic albumin nanoparticles for miRNA delivery (FA-SAN-miRNA) and evaluate their potential for theranostic applications in CCA. Method: FA-SAN-miRNA was synthesized and characterized for size, zeta potential, morphology, magnetic properties, encapsulation efficiency, and drug release. In vitro studies assessed cytotoxicity, cellular uptake, proliferation inhibition in CCA cells (RBE, HuCCT1), and MRI contrast efficacy. In vivo targeting and tracking capabilities were evaluated in a CCA xenograft mouse model. Results: The synthesized FA-SAN-miRNA nanoparticles were spherical, well-dispersed, and superparamagnetic, with a size of 236.25 ± 4.31 nm and a zeta potential of 30.73 ± 5.82 mV. They exhibited high miRNA encapsulation efficiency (88.12 ± 4.63%) and a pH-responsive sustained release profile. FA-SAN-miRNA demonstrated low cytotoxicity, enhanced cellular uptake, and significant inhibition of CCA cell proliferation compared to non-targeted controls. The nanoparticles served as effective T2 contrast agents for MRI. In vivo, FA-SAN-miRNA identifying tumor cells with capture efficiency correlating with tumor burden. Conclusion: The FA-SAN-miRNA platform successfully integrates targeted miRNA delivery, pH-responsive release, and MRI capability, demonstrating potential for identifying tumor cells and targeted delivery in CCA. This multifunctional nanoplatform offers a promising strategy for improving CCA management.