A Dual-Modality MR/PA Imaging Contrast Agent Based on Ultrasmall Biopolymer Nanoparticles for Orthotopic Hepatocellular Carcinoma Imaging

Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer death and early stage diagnosis can greatly increase the survival rate of patient. However, the accurate detection of HCC remains an urgent challenge in medical diagnosis. The combination of magnetic resonance imaging (MRI) and photoacoustic imaging (PAI) are conducive for accurate locating of cancerous tissue. Therefore, it is necessary to explore a more facile and biosafe dual-modal contrast agent for orthotopic HCC detection.

Methods: In this study, a promising contrast agent had been identified based on gadolinium chelated melanin nanoparticles and evaluated its usage as a dual-modal T₁ MRI and PAI contrast agent for orthotopic HCC detection.

Results: The gadolinium-based melanin nanoparticles presented ultrasmall size, high chelation stability and negligible cytotoxicity estimated by CCK-8 assay. Moreover, the nanoparticle exhibited higher r₁ relaxivity (45.762 mM^-1 s^-1) than clinically approved Gadodiamide (4.975 mM^-1 s^-1) at 1.5 T MR scanning. A linear regression analysis confirmed that the nanoparticles were ideal candidates for PAI in vitro. After the nanoparticles were injected into vein in mice with orthotopic HCC, a dramatic increase in signal of the liver was observed at 0.5 hr by MRI and PAI, while the tumor exerted remarkable signal enhancement at 7 hrs, showing excellent detection sensitivity. In addition, the nanoparticles exhibited excellent biocompatibility and they can be excreted through both hepatobiliary and renal pathways after diagnosis.

Conclusion: These results indicate that the ultrasmall gadolinium chelated melanin nanoparticles is a promising candidate as a dual-modal MRI/PAI contrast agent for the detection of orthotopic HCC.