Abstract
Late diagnosis and refractory behavior toward current treatment protocols make pancreatic ductal adenocarcinoma (PDAC) one of the most difficult cancer forms to treat. The imaging-based approach plays an important role to identify potentially curable PDAC patients in high-risk groups at the early stage. In the present study, we developed a core-shell structured gold nanorod (AuNR) as a contrast agent for multimodal imaging and investigated its application for PDAC diagnosis. The composite nanoparticles composed of a AuNR core inside a layer of mesoporous silica that was then coated with a gadolinium oxide carbonate shell (AuNR-SiO2-Gd) are designed to be used in magnetic resonance imaging (MRI), X-ray computed tomography (CT), and photoacoustic imaging (PAI). A phantom study with the AuNR-SiO2-Gd NPs demonstrated higher MRI contrast compared to Gadovist and higher X-ray attenuation than Visipaque. A strong, stable, and broad wavelength range signal with a peak at 800 nm was observed in PAI. The AuNR-SiO2-Gd NPs showed significant contrast enhancement under PAI/MRI/CT in both the liver and spleen of control mice after intravenous administration. The utility in PDAC was studied in a genetically engineered mouse model carrying Kras and p53 mutations, which develops spontaneous tumors and keeps the desmoplasia and hypovascularity feature of PDAC in patients. The AuNR-SiO2-Gd NPs were highly accumulated in the surrounding soft tissues but were sparsely distributed throughout the tumor due to dense stroma infiltration and poor tumor vascularization. Hence, a negative contrast within the tumor area in CT/PAI and a positive contrast in MRI were observed. In conclusion, AuNR-SiO2-Gd NPs have good potential to be developed as a multimodal contrast agent for PDAC, which might improve early diagnosis and benefit the clinical outcome for PDAC patients.