The Synthesis,Performance And Application Of GSH-responsive Au@ZIF-8 In The Integration Of Tumor Diagnosis And Treatment

The near-infrared photothermal conversion material is widely used in the field of cancer diagnosis and treatment for it can simultaneously realize the functions of photoacoustic imaging and photothermal therapy.However,after the near-infrared photothermal conversion material is administered through the tail vein,it is inevitably trapped by the normal tissues of the body,causing signal interference to the diagnosis of the tumor and damaging normal tissues.To solve this problem,we developed intelligent photothermal conversion materials for tumor microenvironment response.Such intelligent photothermal conversion materials are only triggered in the tumor microenvironment,exhibiting the functions of photoacoustic imaging and photothermal therapy.Based on this,we combined the gold nanostructured material and the Zeolitic Imidazolate Framework(ZIF-8)with glutathione(GSH)response characteristics to design and synthesize two zeolite imidazole skeleton coated gold nanostructures(Au @ZIF-8).The trigger mechanism of Au@ZIF-8 mainly consists of two steps,release and self-assembly,which are carried out continuously.Au@ZIF-8 maintains structural integrity in normal physiological environment,but in tumors with high GSH expression,ZIF-8 will degrade and release gold nanomaterials.At the same time,the gold nanomaterials self-assemble in the presence of GSH,and the absorption in the nearinfrared region is enhanced,which can be used for photoacoustic imaging and photothermal therapy.In vitro and in vivo experiments show that Au@ZIF-8 does not produce photoacoustic signals in normal tissues,and only shows obvious photoacoustic signals at the tumor site.In addition,the material can be used for photothermal therapy after being triggered by GSH.This work provides a new diagnosis and treatment strategy for the treatment of tumors,effectively reducing the interference of normal tissue signals on tumor diagnosis and the side effects on normal tissues during treatment.The specific work is as follows:1.The synthesis,performance and application of GSH-responsive Au NP@ZIF-8 in the integration of tumor diagnosis and treatment.Au nanoparticles(Au Nanoparticles,Au NPs)with a particle size of about 25 nm were prepared by seed method.ZIF-8 was coated on the surface of Au NPs to synthesize Au NP@ZIF-8 with good dispersibility.After the material is triggered by GSH,the absorption peak of it shifts from 524 nm to 695 nm,and the absorption at 695 nm can be used for photoacoustic imaging and photothermal therapy.The experimental results show that after the material is triggered,the tumor can be imaged by photoacoustic imaging technology,and the tumor ablation treatment can be realized by photothermal therapy.2.The synthesis,performance of Au NR@ZIF-8 in response to GSH and its application in the integration of tumor diagnosis and treatment in the NIR-II.Based on the first part,we replaced the Au Nanorods(Au NPs)with the Au Nanorod(Au NRs),and used the GSH response of Au NRs to regulate the absorption of the material to near-infrared.The biological window,such as the absorption peak,redshifts from 770 nm to 845 nm.Au NR@ZIF-8 continues to explore based on the GSH trigger response in the near-infrared region with photothermal heating and photoacoustic imaging enhancement,and is expected to build an effective tumor diagnosis and treatment platform...