Synthesis And Application In Magnetic Resonance Imaging Of Zinc Manganese Ferrite Nanoparticles

Thanks to their excellent magnetic properties,good biocompatibility and facile modification on surface,magnetic nanoparticles have broad applications in biomedicine,e.g.targeted drug delivery,magnetic resonance imaging（MRI）,biological separation and magnetocaloric therapy.Zinc manganese ferrite（ZMF）nanoparticles,as a kind of representative magnetic nanoparticles,show significantly shortened T₂relaxation time,which can be applied to distinguish abnormal and normal tissues by amplifying their difference on magnetic resonance signal values.However,there are several issues to be solved before bio-magnetic application,such as oil-water phase transfer,size-controlled synthesis and a lack of specific targeting.This paper focused on size regulation and functional design of ZMF nanoparticles.An efficient MRI contrast agent for the clinical diagnosis and positioning of gliblastoma has been successfully constructed,the main contents include:（1）Size regulation of ZMF nanoparticles:It is hard for ZMF nanaoparticles to meet the needs of different biological applications due to their narrow range of size regulation.In this regard,we have successfully synthesized 5-20 nm ZMF nanoparticles by the regulation of different synthetic parameters（reflux duration,metal precursors and oil phase reducing agents）,which is simpler than the seed-mediated growth and the obtained nanoparticles with well-defined size distribution.It is found that the addition of 1,2-hexadecanediol is beneficial to the formation of size-reduced nanoparticles,while metal chloride and longer reflux time are helpful to prepare enlarged ones.（2）Ultrasmall zinc manganese ferrite（UZMF）nanoparticles as MR imaging nanoprobes:to improve blood-brain barrier（BBB）permeability and targeting-specificity for glioblastoma,we prepared UZMF nanoparticles and coated these hydrophobic nanoparticles with an ultrathin SiO₂ layer using a modified reverse microemulsion approach,which could yield water-soluble UZMF@SiO₂（UZMFS）nanoparticles with much improved biocompatibility.UZMFS nanoparticles showed significantly improved dispersity and stability in aqueous medium due to the rich content of-OH on the surface of SiO₂.Subsequently,angiopep（ANG）,a dual-targeting ligand capable of specially targeting to both glioblastoma and BBB,was grafted on the UZMFS nanoparticles.Compared with Gd-DTPA,the resultant UZMFS-ANG with SiO₂ layer of 1 nm thick,showed an enhanced MRI performance with r₂ value of 240.38mM^-1s^-1 and r₁ value of 4.2 Mm^-1s^-1.Our results suggest that the obtained UZMF@SiO₂-ANG nanoparticles exhibit excellent biocompatibility,enhanced BBB-crossing capability and improved T₂-mode MRI performance for glioblastoma,which provides a possible solution to clinical diagnosis of glioblastoma.