Melanin-manganese nanoparticles with ultrahigh efficient clearance in vivo for tumor-targeting T1 magnetic resonance imaging contrast agent

Abstract

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 Mn²⁺-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 r₁ 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 tumor-bearing 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 T₁ MRI contrast agent for tumor-targeted imaging.