Construction Of Multimodal Nanoprobe Based On Fe(Ⅲ) Biomineralization And Its Application In Tumor Diagnosis And Treatment

Cancer is one of the main diseases threatening human health and life.At present,the problem which tumor treatment facing on is the lack of methed to make accurate diagnosis on the early stage of tumor and effective clinical treatment or prognosis,which led to a high cancer mortality.Therefore,designing new tumor diagnosis and treatment drugs has become the most important tasks of the accurate tumor diagnosis and treatment.In recent years,with the development of nanotechnology,nano-materials have had more and more extensive application in the field of tumor diagnosis and treatment because of its in aspects such as sound,light,magnetism,thermal unique properties,especially nanoprobes which combine many functions of tumer diagnosis and treatment have irreplaceable advantages in the early diagnosis and warning of metastasis and prognosis of tumor after treatment.However,due to the complexity of tumor microenvironment,most of the current nanomaterials have the defects of low diagnostic sensitivity,poor specificity,and large toxic on normal tissues.Therefore,the development of sensitive imaging and specific treatment of tumor diagnosis and treatment with the integration of nano-probe has become a new direction of accurate diagnosis and treatment of tumor.The first part of this paper focuses on the realization of accurate diagnosis and treatment of tumors,we designed and constructed a kind of tumor microenvironment responsive"intelligent"integrated diagnosis and treatment nanoprobe.On this nanoprobe,bovine serum albumin（BSA）was adsorbed on the surface of Fe₃O₄nanoparticles as a"protein crown",and tannic acid（TA）-Fe（Ⅲ）was loaded on the surface of BSA,which has the ability to release in acidic microenvironment.Then the"core-shell"structure of the nanoprobe was constructed.The experimental results show that the nanoprobe has good stability and biocompatibility.Due to the Fe unsaturated coordination in TA-Fe（Ⅲ）,when the probe enters the blood and binds to transferrin,it can proactively target the transferrin receptor overexpressed on tumor cell membran.When the probe entered the tumor tissue,Fe³⁺was released due to the acidic microenvironment（T₁imaging）.Due to the uneven pH distribution in tumer tissue,the release rate of iron ions was different,which lead to different T₁signal value.However,the T₂imaging effect of Fe₃O₄was not affected by pH.Thus,it can achieve accurate visualization of the tumer tissue.In terms of treatment,the good photothermal effect and targeting ability of TA-Fe（Ⅲ）,as well as the"Ferroptosis"anti-tumor effect of the released Fe³⁺,were utilized to solve the problems of insufficient targeting and poor therapeutic effect of PTT photothermal agent in clinical practice.Then,we hope to realiz the MRI diagnosis of tumor and the photothermal/"Ferroptosis"collaborative treatment.In the second part of this paper,based on the exploration of the properties of polyphenol-iron complexes in the previous work,we developed a novel ¹⁸F labeling method by using the vacant coordination site of unsaturated coordination Fe³⁺to complex radioactive ¹⁸F.By linking polyphenol-Fe（Ⅲ）complexes with different tumor-specific targeting molecules,¹⁸F labeling of different targeting molecules can eventually be achieved.In this section,we took gallate（GA）as an example.Based on polyphenol-Fe（Ⅲ）,one of its end was covalently bound to c（RGDfk）,then the other end was complexed with¹⁸F by the unsaturated coordination bond on the polyphenol-Fe（Ⅲ）complex.Though this way,we designed a novel ¹⁸F-labeled PET tumor targeting probe.This method is expected to provide a new idea for the construction of targeting PET probes.In summary,in this paper,we achieved sensitive imaging and targeted treatment of tumors through a intelligent pH-responsive integrated diagnosis and treatment nanoprobe and a novel PET nanoprobe ¹⁸F labeling strategy based on polyphenol-Fe（Ⅲ）,which provided a new idea for tumor diagnosis,treatment and prognosis.This method was expected to improve the therapeutic effect and survival rate of patients.We think it have great scientific research value and social significance.