Artificially Designed And Synthesized Iron-based Magnetic Nanoparticles As High-performance Probes For Magnetic Medical Imaging

Modern medical imaging technology plays an increasingly important role in biomedical applications.Imaging probe is a crucial part of medical imaging and its property is one of the key factors to determine the imaging effects.In recent years,nanomaterials that possess superior physicochemical properties have been widely used in the development of medical imaging probes.Among them,iron-based magnetic nanoparticles own tunable magnetic properties,excellent biocompatibility and are easy to modification,showing great advantages in the field of medical imaging.According to the imaging principle and the needs of disease diagnosis,controling the characteristics of iron-based magnetic nanoparticles via ingenious chemical design,such as size,shape and surface modification,is a crucial way to improve imaging performance and endow them with versatility.How to design and synthesize iron-based magnetic nanoparticles to improve their imaging effect in living system is one of the research foci in the field of medical imaging.Magnetic resonance imaging(MRI)offers high soft-tissue resolution and unlimited depth penetration without using radiotracers,which has been widely used in clinical tumor diagnosis.The tumorigenesis and progression are accompanied by a series of complicated pathological changes in tumor microenvironment.Therefore,it is critical to develop imaging approaches that can non-invasively and real-time detect tumor pathological biomarkers,and meanwhile obtain tumor anatomical information.The traditional MRI can determine the position and anatomical details of tumors,but they are difficult to reveal the tumor pathological features.Herein,we designed an iron-based magnetic dual-mode nanoprobe,which showed highly sensitive K⁺specific fluorescence imaging and T2-weighted MR contrast effects.The nanoprobes provided anatomical information of tumors at the tissue level,on the other hand,they offered pathological features in tumor microenvironment at the ionic level.To prepare the iron-based K⁺specific fluorescence/MRI dual-mode nanoprobes(KDMNs),firstly,the monodispersed iron oxide nanoparticle(IONP)was synthesized by thermal decomposition method,followed by surface-modifying with mesoporous silica nanoshell(MSN)to improve the water dispersibility and biocompatibility.Then,commercial K⁺indicators were encapsulated into the hollow cavity of IONP@MSN,which was subsequently coated with a K⁺-selective membrane to obtain the KDMN.After systemic administration,KDMNs could readily accumulate in tumors and enhance the MRI contrast between tumor sites and surrounding normal tissues to acquire spatial information of the tumor lesions.Meanwhile,the elevated extracellular K⁺concentration([K⁺]_ex)in malignant tumors triggered a significantly enhanced fluorescence signal,in sharp contrast to benign tumors with normal[K⁺]_ex.Moreover,the cascaded logic operation that we constructed enabled a self-confirmation of dual-modal imaging results acquired from KDMN-enhanced MRI and fluorescence imaging,and thus allowed for non-invasive imaging of tumor malignancy.Magnetic particle imaging(MPI)is an emerging medical imaging method via directly collecting signals from the nonlinear magnetization of the magnetic nanoparticles,which is irradiation-free and characterized by high sensitivity and signal-to-noise ratio.Based on the principal theory of MPI,by tuning the structure of IONPs,we prepared a series of spherical and cubic IONPs with different sizes.Compared with spherical IONPs,cubic IONPs have less disordered spins,which are conducive to obtain larger saturation magnetization and higher magnetic susceptibility,thus showing superior MPI performance.The results demonstrated that the MPI signal of cubic IONPs with an edge length of 22 nm(CIONs-22)was significantly stronger than that of IONPs with other shape and size.The signal intensity generated by CIONs-22 was 4.15-fold higher than that of the commercialized Vivo Trax.Moreover,CIONs-22exhibited efficient cellular internalization by bone mesenchymal stem cells(BMSCs).Also,they were biocompatible and showed no negative effects on the proliferation as well as differentiation of BMSCs.In vivo imaging results demonstrated that MPI of CIONs-22 labeled-BMSCs was highly sensitive,and as few as?2500 cells could be clearly visualized when labeled with CIONs-22.Based on the MPI-CT dual modal imaging,CIONs-22 enabled long-term monitoring of the spatiotemporal migration and distribution pattern of stem cells transplanted to hindlimb ischemia mice.By engineering the surface modification,size and shape of IONPs,we developed a series of biocompatible iron-based imaging probes,which were applied to magnetic medical imaging(including MRI and MPI)to improve imaging sensitivity and specificity,providing novel strategies for highly efficient and non-invasive tumor malignancy identification and stem cell tracking.We expect that these approaches can open a new era for developing next-generation high-performance imaging probes.