Efficient And Safe Manganese-based Magnetic Resonance Contrast Agent

The imaging performance of magnetic resonance imaging contrast agents mainly depends on the physico-chemistry properties of magnetic nanoparticles,including:size,magnetic properties,surface chemistry?hydrophilicity,metal chemical state?,targeting,and biocompatibility.An ideal contrast agent should be controllable in size,high relaxivity,enhanced hydrophilicity,tumor targeting,long circulation time and appropriate biocompatibility.Therefore,the KMnF₃ contrast agent prepared by our research group was further processed.The"top-down"fabrication technique is an important physical technique for nanomaterial processing,which transforms large-sized nanoparticles into small-sized particles by physical method.Here,we used plasma technique to surface reform and size reduction of chemically prepared KMnF₃ particles.The main work includes:?1?KMnF₃ nanocrystal?22nm?was post-treated using a plasma technique to cause severe defects,leading to appropriate water dispersibility and high relaxivity.Severely defective KMnF₃ nanocrystal?SD-KMnF₃?has characteristic high tolerance,as evidenced by cytotoxicity on the macrophage cell,and acute and subchronic toxicity on the healthy mouse.As applied to MR imaging of the allograft orthotopic model of liver cancer,SD-KMnF₃ significantly improved the tumor's contrast-to-noise ratio?P<0.01?,compared with those of two commercial hepatobiliary contrast media?Gd-EOB-DTPA and Mn-DPDP?.?2?Home-made oxygen plasma generator fragments larger KMnF₃ nanoparticle?22nm?into smaller?3-5nm?particle with enhanced hydrophilicity,and high relaxivity and appropriate biocompatibility.The ultrasmall NP has very long circulation time,as its blood half time is around 20 hours.The blood half time of the 22 nm KMnF₃ nanocrystals is 2hours.Compared with the KMnF₃ nanocrystals before treatment,the blood half time of the treated particles is extended by 10 times.When applied as a contrast enhancer for MR imaging of patient-derived tumor xenograft model,which greatly shortens relaxation time of the tumor.In this paper,KMnF₃ contrast agents with severe defects and ultrafine particles are obtained by using the"top-down"technique of oxygen plasma,which have better imaging and targeting,compared with those of two commercial hepatobiliary contrast media.It is of great significance for the clinical diagnosis of tumors.