Construction Of Platinum,Iron And Manganese Bio-nanocomposites And Its Application In Tumor Diagnosis And Treatment

In recent years,the chemically disordered face-centered cubic(fcc)iron-platinum nanoparticles(FePt NPs),as a kind of special nanomaterial with intrinsic magnetism,have been increasingly researched and applied in information storage,biosensors,bioseparation and bioimaging.Especially,the FePt NPs has shown great applied potential in theranostic of tumors.It is well know that the cancer cells have a specific microenvironment that involving acidity(pH=5～6)and the overproduction of hydrogen peroxide(H2O2).Therefore,based on the Fenton reaction and ferroptosis mechanism,the high-active Fe2+ could be released from FePt NPs to catalyze intracellular H2O2 into reactive oxygen species(ROS,such as hydroxyl radicals(·OH)),which could strongly oxidize various organic molecules including membrane lipids,DNA and proteins and ultimately induce ferroptosis of cancer cells.In addition,the multifunctional nanomaterials that combined with imaging diagnostic methods,such as magnetic resonance(MR)and computed tomography(CT)imaging,have received extensive attention and research.The MR imaging,with high accuracy,non-invasiveness and real-time monitoring,was widely applied in cancer diagnosis.The Fe in FePt NPs was a commonly used T2-weighted imaging(dark areas)contrast agent with high T2 relaxation rate for tumor imaging.However,there was often confused signals from other surrounding biological tissues such as hemorrhage and blood clots of T2-weighted imaging and resulted in poor imaging effect.Fortunately,the Mn-based composites,as an emerging T1/T2 weighted contrast agent,have been widely used due to their high safety,low toxicity and high contrast.Here,based on the advantages of FePt NPs and Mn-containing composites,the following work was mainly carried out:Firstly,the hydrophobic FePt nanocubes(FePt NCs)with size of 11-12 nm were synthesized by thermal decomposition and thermal reduction.Then,the FePt@MnO hetero-nanoparticles(FePt@MnO NPs)were obtained by seed-mediated and in-situ growth method that using FePt NCs as seeds and manganese oleate as precursor.The morphology,structure and magnetic properties of the synthesized FePt NCs and FePt@MnO NPs were detected by TEM,HR-TEM,XRD,EDS mapping and hysteresis loops,which all proved that the FePt NCs and FePt@MnO NPs were successfully synthesized.After the amphiphilic small molecule polymer 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-[(polyethylene glycol)5000]-folic acid(DSPE-PEG5000-FA)was coated on the surface of FePt@MnO NPs by solvent-exchange method,the bio-nanocomposites(FePt@MnO)@DSPE-PEG5000-FA(FMDF NPs)with excellent biocompatibility and targeting were obtained.The UV-vis absorption spectroscopy,FTIR spectroscopy,Zeta potential and negative staining with phosphotungstic acid all proved that DSPE-PEG5000-FA was successfully coated on the surface of FePt@MnO NPs.Afterwards,in vitro cell experiments,such as ROS fluorescence assay,cytotoxicity assay and Prussian blue staining,demonstrated that FMDF NPs could effectively induce the produce of ROS and finally induce apoptosis to cancer cells while no damage to normal cells.In vivo tumor imaging diagnosis and inhibition experiments with balb/c tumor-bearing mice indicated that FMDF NPs have excellent ability of MR/CT dual-mode imaging diagnosis that the tumor was obviously distinct from the surrounding tissue,and the growth of tumor significantly inhibited while no adverse effects on other important organs.Therefore,the FMDF NPs,as an integrated nanomedicine with simultaneous MR/CT dual-modality imaging diagnosis and ferroptosis anticancer chemotherapy,will play an important role in clinical applications.