Responsive Manganese Based Magnetic Resonance Imaging Nanoprobe For Tumor Diagnosis And Treatment

Malignant tumor is a serious threat to human health and life.The personalized treatmentof tumors largely depends on the early and accurate diagnosis of tumors.Molecular imaging technology has a broad application prospect in monitoring the pathological deterioration and metastasis of tumors in the early stage of development.Molecular Imaging techniques include Ultrasound Imaging,Photoacoustic Imaging,X-ray Computed Tomography,Positron Emission Computed Tomography,Magnetic Resonance Imaging(MRI),etc.Among them,magnetic resonance imaging has high resolution and no radioactivity in soft tissue,which can realize a variety of imaging modes,and plays an important role in the early accurate diagnosis of tumors.The use of MRI contrast agents can better distinguish between normal and diseased tissue.At present,the main clinical contrast agents are various gadolinium ion complexes,such as Magnevist,which have the disadvantages of low relaxation rate and no specificity for tumor.Therefore,the design of responsive magnetic resonance imaging nanoprobe with good stability and sensitive response to tumor microenvironment is an urgent scientific problem to be solved.In addition,the realization of tumor diagnosis and treatment at the same time will play an important role in promoting the development of nanomedicines.In this paper,a responsive Mn-based magnetic resonance imaging nanoprobe was designed and synthesized,and the responsive performance of the nanoprobe was utilized to achieve accurate diagnosis and multi-mode treatment of solid tumors and millimeter liver metastases.The main innovation points and research contents are as follows:1.A pH-activatable MnCO₃ nanoparticle for improved magnetic resonance imaging of tumor malignancy and metastasisThe MnCO₃ nanorhombohedras(MnNRs)with pH response properties were designed.The method of one-step precipitation of Mn²⁺and CO₃^2-in reverse microemulsion is simple.The prepared MnNRs were further modified with PEG,which made the nanoparticles have good biocompatibility and targeting.At the same time,PEG coating can shield the contact between the surface of nanoparticles and water particles to inhibit the relaxation rate of MnNRs and make the MRI signal"turn off".MnNRs respond to the slightly acidic environment of the tumor,acid decompose manganese ions,and the MRI signal"turn on".Manganese ions bind to the surrounding proteins nonspecifically,which prolongs the rotation correlation time and further amplifies the MRI signal.This method provides a new idea for the early accurate diagnosis of tumors and metastases.2.Application of pH/GSH dual responsive Mn₃O₄ nanoparticles in tumor diagnosis and treatmentMn₃O₄ tetragonal bipyramids(Mn TBs)with the double response of pH/GSH were designed.The nanoprobe responds to the tumor pH/GSH environment and specifically lights up MRI signals.Accurate diagnosis of solid tumors and millimeter liver metastases was achieved.The degraded Mn²⁺catalyzes H₂O₂ to produce·OH,which can kill tumor cells and realize tumor therapy with Chemodynamic Therapy(CDT).At the same time,the Pt(IV)prodrug in the constructed nanoprobe was reduced to cisplatin molecule by GSH,which further improved the therapeutic effect of tumor through chemotherapy.Nano-probe has a longer blood circulation time and higher tumor enrichment rate without obvious toxic and side effects.This method can accurately diagnose and effectively treat solid tumors and liver metastases.