Design Of Transition Metal Hybrid Nanoprobe And Its Application In Tumor Diagnosis And Treatment

Cancer is one of the major diseases that seriously endanger human health and life.The current clinical treatment methods are mainly chemotherapy and radiotherapy.However,their treatment effect is unsatisfactory.In addition,a single treatment method is usually difficult to eliminate tumors,and combined treatment can effectively avoid the shortcomings of single treatment,achieve synergistic effects,and eventually improve treatment effects.The diagnosis of cancer is the key to the prevention and treatment of cancer.Biomedical imaging is a reliable tool for the diagnosis of human diseases.Generally,a single imaging method is difficult to provide comprehensive information on the lesion.Multimodal imaging can significantly improve the sensitivity and resolution of imaging,and provide more detailed anatomical and biological information.Therefore,in order to significantly improve the treatment effect,real-time monitoring of the treatment process and reduce the damage to healthy tissues,it is of great significance to integrate multimodal imaging and combined therapy into a platform.Nanomaterials with special properties have been extensively studied in the diagnosis and treatment of tumors.And,they can be passively enriched in tumors through enhanced permeability and retention(EPR).The construction of multimodal imaging-guided combination therapy nanoprobes has good application prospects.Furthermore,nanomaterials as carriers can significantly extend blood circulation time,reduce side effects,and increase the amount of the drug reaching the tumor site.Transition metals such as manganese and iron are elements contained in organisms.Nanomaterials based on manganese and iron have high biological safety and have been widely studied in the diagnosis and treatment of tumors.In general,it is difficult for single-component nanomaterials to achieve multimodal imaging-guided combined therapy.Hybrid nanomaterials can break through the limitations of single-component materials,which is of great significance in the field of biomedicine.In this paper,we design and synthesize hybrid nanoprobes based on transition metals(iron and manganese),and explore the applications of these probes in drug loading,multimodal imaging,and combination therapy.The specific content is summarized as follows:1.We synthesized a multifunctional hybrid nanoprobe based on manganese dioxide nanosheets coated dopamine nanospheres(PDA@ut-MnO2),which can be used as a carrier to effectively load the photosensitizer methylene blue(MB).The obtained PDA@ut-MnO2/MB nanoprobe have good biocompatibility and photothermal effect.The MnO2 nanosheets not only serve as an effective carrier to load MB,but also regulate the tumor microenvironment and promote photodynamic therapy by consuming excessively high concentrations of glutathione(GSH)and producing oxygen,and the obtained Mn(Ⅱ)ions effectively realize the magnetic resonance imaging(MRI),and they are metabolized by the kidneys,which greatly reduce the potential biological toxicity of nanomaterials.Under the irradiation of 650 nm laser,a large amount of singlet oxygen(1O2)was produced by the loaded photosensitizer MB,which effectively realized the photodynamic therapy.Both cell experiments and in vivo experiments indicate that the hybrid nano-probe realizde a better therapeutic effect by photothermal and photodynamic therapy than the single treatment.2.In the previous work,tumors were treated effectively by constructing photothermal nanocarriers loaded with photosensitizers.However,the single imaging method and the tissue penetration depth of 650 laser can be further solved and optimized.On this basis,noble-metal@FexOy core-shell nanoparticles(Au@FexOy AuRu@FexOy,AuPt@FexOy and AuPd@FexOy)are one-pot constructed by a simply redox self-assembly strategy.As a typical example,AuPd@FexOy nanoparticles are applied for oncotherapy,AuPd@FexOy nanoparticles can be activated by a small amount of NaBH4 and the obtained products r-AuPd@FexOy nanoparticles obviously enhance the productivity of hydroxyl radical in subsequent Fenton reaction for chemodynamic therapy.In addition,the r-AuPd@FexOy nanoparticles with good photothermal conversion properties not only realize photothermal therapy,but also further promote the generation of hydroxyl radicals.Moreover.the r-AuPd@FexOy nanoparticles also have pH-responsive MRI property,CT imaging capacity,regulation the tumor microenvironment function.In summary,the nanoprobe can complete MRI/CT imaging guided the photothermal/photothermal enhanced chemodynamic synergistic therapy.In vivo experiments showed that the r-AuPd@FexOy nanoparticles could significantly inhibit the growth of tumor.3.On the basis of the previous work,in order to further improve the effect of tumor treatment and reduce the damage to the surrounding healthy tissue.Here,a stimulus-responsive intelligent nanoprobe was synthesized,which could be activated under specific conditions to effectively realize MRI/photoacoustic imaging/fluorescence imaging guided the chemotherapy/photothermal/chemodynamic synergistic therapy.The specific steps were as follows:AuPd@MnxOy nanoparticles with Jauns structure were prepared by a simple method,and their surface are coated by lauric acid and futher loaded with the chemotherapy drug doxorubicin(DOX)to obtain AuPd@MnxOy@L/DOX nanoprobes.When the probe reaches the tumor site,it can produce a large amount of 1O2 and release the chemotherapy drug DOX under the irradiation of laser and in the acidic microenvironment,so as to effectively kill the cancer cells.In addition,good photothermal conversion ability realize efficient photothermal therapy.The nanoprobe can also realize real-time monitoring of the treatment process through pH-responsive MRI,photoacoustic imaging and fluorescence imaging.The A549 subcutaneous mouse tumor model was established,and the experimental results showed the intelligent nanoprobe had good selectivity and can destroy tumor more efficiently and specifically,which was a potential tumor diagnosis and treatment agent.