The Application Of Multi-targeted Magnetic Polydopamine In Multi-modal Imaging And Multi-treatment For Precise Tumor Treatment Research

Nowadays,despite the continuous development and progress of science,malignant tumors which is still the second leading cause of death in the world.And the ears and effective treatment are important to the successful treatment of cancer.Nanotechnology,as a relatively young subject,has rapidly integrated into the current oncology treatment.Moreover,compared with the insufficient drug concentration at target site,low bioavailability,high toxicity of traditional anti-tumor treatment,new nanoparticles could act as a nanoplatform that can reduce the toxicity of drugs and its nano structure could realized the combination of variety kinds of diagnosis and treatment,which can effectively improve the therapeutic effect and reduce side effects.So the precise theranostics of the tumor site is of great interests and difficult point to the investigators.In this study,we have design a novel theranostics nano-platform based on magnetic polydopamine(MPDA)coated with hyaluronic acid-methotrexate conjugates(MPDA@HA-MTX)to apply for chemo-photothermal treatment.In this nano-platform,HA-MTX conjugates could offer specific cellular dual-targeting ability to folate receptor and CD44 receptor,while MPDA is used as a versatile carrier for the loading of drug doxorubicin(DOX),to achieve controlled release and photothermal treatment(PTT)simultaneously,and Fe3O4 served as the core is applied as contrast agent for T2-weighted magnetic resonance imaging(MRI)and early-phase magnet targeting.Evaluate the prepared HA-MTX conjugates magnetic polydopamine loaded DOX comprehensively through characterizing the size,morphology,zeta potential and magnetic characterization of nanoparticles,and determining the intracellular drug uptake and cell toxicity,bio-distribution,imaging effect,body toxicity and anti-tumor efficacy were investigated as well.As the expesimental results showed,the magnetic nanoparticles prepared by a co-precipitation method had a diameter of about 5 nm,and the super paramagnetic properties of the nanoparticles were excellent by measuring their hysteresis curves.And the hyaluronic acid and methotrexate conjugates modified magnetic polydopamine nanoparticles also have excellent superparamagnetic property.The particle size of our nanoparticles are about 236.5+21.54 nm,and the zeta potential is-22.5 + 0.4 mV,which have great photothermal conversion efficiency and great thermal stability.Doxorubicin,a chemotherapeutic drug,could be loaded into the polydopamine layer by ?-? stacking,and the nanoparticles have a high loading capacity.Under the acid and laser irradiation condition,the drug releasing amount is of 7 times as much as that under the neutral solution and without light laser condition.The results of the vitro test also showed that the HA-MTX conjugates modified magnetic polydopamine nanoparticles could target to HeLa cells.While the in vivo imaging results of animal showed that it had good tumor targeting and imaging effect to tumor-bearing mice.The diagnosis and treatment could be achieved simultaneously,we could monitor the drug distribution through the imaging function,and when nanoparticles were gathered in the tumor site,laser irradiation was supplied to tumor site,which could not only promote the release of drugs,but also has the effect of photothermal therapy.Therefore,the nanoparticles can ultimately achieve the precise theranostics of the tumor.In summary,the multifunctional prepared hyaluronic acid and methotrexate conjugates modified magnetic polydopamine nanoparticles can realize multistage targeting,magnetic targeting and cellular targeting,drugs release under photothermal treatment,multi-model imaging of fluorescence imaging and magnetic resonance imaging(MRI),combined therapy of chemotherapy and photothermal therapy.Compared with the traditional administration mode,the nanotechnology greatly improves the drug targeting ability,the control of drug release and multimodal imaging ability in diagnosis and treatment.It could be regard as one of great step forward to the process to achieve accurate treatment of tumor,and also provide a valuable reference for researchers in the field.