Nanoscale Metal Organic Coordination Polymers For Application In Tumor Imaging And Treatment

Cancer is one of the major diseases that endanger human health.Traditional clinical treatment methods are mainly surgery,chemotherapy,and radiotherapy.However,these treatment methods have their own limitations,such as limited therapeutic effect,large side effects,drug resistance,and so on.It is necessary to develop new cancer treatment methods.Nanomaterials play an important role in cancer therapy because of their special physical and chemical properties.For example,the large specific surface area of nanomaterials can be used as drug carriers to achieve highly targeted enrichment of drugs in tumor sites.On the other hand,the optical,magnetic,acoustic,and X-ray properties of the material itself can be used for imaging-guided cancer treatment to improve the therapeutic effect and achieved high-efficiency and accurate treatment.However,the in vivo long-term retention of some functional nanomaterials greatly limits their bioapplication.It 1s great necessary to develop biodegradable functional nanomaterials for high efficient and low toxicity treatment of tumors.Nano-sized metal-organic frameworks(NMOFs)and metal-organic coordination polymers(NCPs)using metal ions and organic ligands to form coordination network structures have excellent physical/chemical diversity and biodegradability.They have played an important role in cancer imaging and treatment in recent years.In this paper,nanosized metal-organic coordination polymer nano-materials are constructed to be used in cancer imaging/detection and tumor therapy,and to achieve high efficiency and low toxicity in the diagnosis and treatment of tumors.The main research contents are summarized as follows:1.The redox-sensitive metal-organic coordination polymer Mn-SS/DOX@PDA-PEG nanomaterials have been developed for cancer diagnosis and treatment.The redox-sensitive metal-organic coordination polymer nanomaterials based on manganese ion and dithiodiacetic acid were synthesized by solvothermal method.The obtained manganese ion-dithiodiacetic acid(Mn-SS)has mesoporous structure,which makes it capable of loading the chemotherapeutic drug doxorubicin(DOX).The disulfide bond(SS)contained in dithiodiacetic acid can be broken in the presence of glutathione(GSH),leading to the disintegration of the whole nanomaterial structure and the controlled release of chemotherapeutic drugs.Meanwhile,the manganese ions in the redox-sensitive metal-organic coordination polymer system have T1 magnetic resonance imaging function.Cellular and animal levels have achieved a good therapeutic effect of chemotherapy.At the same time,the organic coordination polymer was rapidly degraded in vivo,which greatly improved the biological safety of the carrier.2.A metal-organic coordination polymer HRP@Mn-ABTS-PEG nanoprobe has been developed for high sensitivity photoacoustic imaging and detection of hydrogen peroxide(H2O2)in tumors.Horseradish peroxidase@manganese ion-2,2,-diazo-bis-3-ethylbenzothiazoline-6-sulfonic acid(HRP@Mn-ABTS-PEG)nanoparticles were synthesized by one-step method.When HRP@Mn-ABTS-PEG particles react with H2O2,ABTS is oxidized to ABTS form,which produces strong absorption at 700-900 nanometers,so it can be used for photoacoustic imaging.At the same time,the organic coordination polymer HRP@Mn-ABTS-PEG nanoprobe containing Mn2+can be used for T1 magnetic resonance imaging.High sensitivity detection of hydrogen peroxide was achieved in CT26 subcutaneous tumor model and T24 bladder cancer model by various administration methods(i.t.injection,intravesical instillation and i.v.injection).The magnetic properties of the probe also enable magnetic resonance imaging of tumors.The two imaging methods are combined to provide more abundant imaging information.At the same time,using the degradable function of metal-organic coordination polymer,it can be metabolized in vitro through feces and urine after tail vein injection,which greatly reduces the toxicity of nano-materials caused by long-term detention in vivo.In this master's thesis,two kinds of metal-organic coordination polymer nanomaterials based on manganese ions were constructed for cancer treatment and imaging/detection.The results of this study have some important reference value and reference significance in metal-organic polymer materials.