Commercial contrast agents demonstrated release risk of the toxic gadolinium ions, and designing of highly stable complexes of biogenic element such as Mn is challenging. In this contribution, Mn‐melanin nanoparticles have been prepared and reacted with m‐PEG. The effect of initial amount of Mn ions on the Mn absorption and its release by melanin nanoparticles (MNP) has been investigated. It has been found that MNP absorb and release more Mn ion by increasing the initial amount of Mn ions. It has been found that time and temperature has no significant effect on Mn absorption by MNP. It is found that the hydrodynamic size of MNP is in accordance with size of MNP which measured with TEM analysis (5.5±2 nm) and the effect of chain of m‐PEG and conformational alteration of MNP is responsible of hydrodynamic size variation. The zeta potential of MNP is decreased by PEGylation and reaction with Mn ions. MNP−Mn‐PEG demonstrated low toxicity up to 3.45 mg/mL after 24 h for human embryonic kidney cells. Finally, the r1 value of MNP−Mn‐PEG is 10 fold higher than Dotarem as the commercial MRI contrast agent which can be administrated at much lower doses to achieve similar contrast of Dotarem.
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