Melanin-manganese nanoparticles with ultrahigh efficient clearance in vivo for tumor-targeting T_1 magnetic resonance imaging contrast agent

摘要

Endogenous biomaterials in organisms, with native biocompatibility and biodegradability, appear more advantageous in the development of nanoscale diagnostic and therapeutic systems for future clinical translation. Herein, a novel tumor-targeting Magnetic Resonance Imaging (MRI) contrast agent was developed based on Mn~(2+)-chelating ultrasmall water-soluble melanin nanoparticles (MNP-PEG-Mn). The nanoparticles, with a size of about 5.6 nm, presented high chelation stability and showed negligible cytotoxicity as estimated by MTT assay. Moreover, the r_1 longitudinal relaxivity (20.56 mM~(-1) s~(-1)) of MNP-PEG-Mn was much higher than that of Gadodiamide (6.00 mM~(-1) s~(-1)), which is a clinically approved MRI contrast agent. In vivo MRI experiments revealed excellent tumor-targeting specificity after tumorbearing mice were intravenously injected with MNP-PEG-Mn. Additionally, MNP-PEG-Mn could be excreted via renal and hepatobiliary pathways with negligible toxicity to body tissues. These preliminary results indicated the clinically translatable potential of MNP-PEG-Mn as a T_1 MRI contrast agent for tumor-targeted imaging.