Jinghua Sun,1,2,* Xiaoyan Li,2,* Anqi Chen,2,* Wenwen Cai,2 Xiaoyang Peng,1 Liping Li,3 Bo Fan,3 Lingjie Wang,2 Huanhu Zhang,4 Ruiping Zhang2
1Center for Translational Medicine Research, Shanxi Medical University, Taiyuan 030001, People’s Republic of China; 2Imaging Department, The Affiliated Da Yi Hospital of Shanxi Medical University, Taiyuan 030000, People’s Republic of China; 3Shanxi Medical University, Taiyuan 030001, People’s Republic of China; 4The Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan 030000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Ruiping Zhang
The Affiliated Da Yi Hospital of Shanxi Medical University, No. 99, Longcheng Street, Taiyuan, Shanxi 030000, People’s Republic of China
Email zrp_7142@sxmu.edu.cn
Huanhu Zhang
The Affiliated Tumor Hospital of Shanxi Medical University, No. 3 ZhiGongXinCun, Taiyuan, Shanxi 030000, People’s Republic of China
Email Zhhh31@163.com
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.
Keywords: melanin nanoparticles, gadolinium, magnetic resonance imaging, photoacoustic imaging, orthotopic hepatocellular carcinoma
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