Pharmacokinetics study of Zr-89-labeled melanin nanoparticle in iron-overload mice

Melanin, a natural biological pigment present in many organisms, has been found to exhibit multiple functions. An important property of melanin is its ability to chelate metal ions strongly, which might be developed as an iron chelator for iron overload therapy. Herein, we prepared the ultrasmall water-soluble melanin nanoparticle (MP) and firstly evaluate the pharmacokinetics of MP in iron-overload mice to provide scientific basis for treating iron-overload. To study the circulation time and biodistribution, MP was labeled with 89Zr, a long half-life (78.4 h) positron-emitting metal which is suited for the labeling of nanoparticles and large bioactive molecule. MP was chelated with 89Zr directly at pH 5, resulting in non-decay-corrected yield of 89.6% and a radiochemical purity of more than 98%. The specific activity was at least190 MBq/μmol. The 89Zr-MP was stable in human plasma and PBS for at least 48 h. The half-life of 89Zr-MP was about 15.70 ± 1.74 h in iron-overload mice. Biodistribution studies and MicroPET imaging showed that 89Zr-MP mainly accumulated in liver and spleen, which are the target organ of iron-overload. The results indicate that the melanin nanoparticle is promising for further iron overload therapy.