COF-based Nanoreactors For The Study Of Enhanced Tumor Photothermal Therapy

Despite the continuous development of modern medical technology,cancer poses a serious threat to human health worldwide.Cancer is difficult or impossible to cure because it involves various genetic changes and cellular abnormalities.In addition,its complexity and heterogeneity promote aggressive growth of cancer cells,leading to significant morbidity and mortality.The three traditional approaches to cancer treatment include surgery,radiation therapy,and chemotherapy.However,due to severe surgical trauma,non-specific and excessive radiation,and the irreplaceable deficiencies of these therapies in terms of targeting,biocompatibility,multidrug resistance,and drug accumulation,patients may experience serious physiological side effects,resulting in poor quality of life and difficulty in achieving the desired therapeutic effect.These therapeutic deficiencies have inspired the development of new,precise,and more effective oncology treatment strategies.For example,several emerging treatments such as photodynamic therapy（PDT）,photothermal therapy（PTT）,and photoacoustic therapy have improved or may improve treatment outcomes.In addition to directly ablating tumors,the heat generated in the PTT process can also achieve the on-demand release of other therapeutic compounds,regulate gene transcription and enzyme activity,and enhance the chemical reaction of tumor tissues,so as to achieve photothermal synergy anti-cancer,which can overcome the obstacles of single-mode therapy,often producing a super additive effect,called"1+1>2",this multi-modal therapy has remarkable efficacy,therefore,through physical adsorption or chemical combination of different types of therapeutic agents combined in a single nanostructure to construct multifunctional nanomaterials,Multimodality collaborative therapy for creating tumors.Covalent organic frameworks（COFs）are a class of organic crystalline porous materials discovered in the early 21st century,which have become an attractive emerging class of materials due to their high crystallinity,inherent porosity,structural regularity,multiple functions,design flexibility and excellent stability.The study found that COF has good biocompatibility and negligible systemic toxicity,so it is a promising nanodrug delivery platform in cancer treatment.Based on the current status of tumor treatment and considering the advantages of COFs in biomedicine,this thesis carries out research work from the following aspects.In the first chapter of this thesis,the types of COF based on different bonds,the applications and challenges of COF as nanodelivery systems in biomedicine,and the advantages and disadvantages of photothermal nanomaterials that are currently widely used.In the second chapter,the design and synthesis of GOx@COF-ICG nanomaterials,which is a COF-based nanoreactor,ICG has a high photothermal conversion rate,after loading glucose oxidase,it can inhibit the photothermal ablation defense mechanism in vivo by reducing the content of ATP and HSP in vivo,and at the same time synergistic with starvation therapy to enhance photothermal ablation and achieve better therapeutic effects.In the third chapter,COF@Ca O₂-HA nanomaterials were designed and synthesized,and a nano COF with photothermal properties was successfully obtained by solvothermal method,and Ca O₂and HA were generated in situ on COF,HA has good biological targeting,and Ca O₂can react with water in the tumor interstitial fluid in the tumor acidic microenvironment,resulting in cytotoxic H₂O₂and calcium ion accumulation,and alleviating the hypoxic environment in the tumor.At the same time,the consumption of extratumor interstitial fluid is conducive to the penetration of nanomaterials into the tumor site,and is conducive to the better exertion of photothermal effect of materials.COF as a hot organic nanomaterial in recent years,itself has irreplaceable advantages,but COF in biomedical application exploration has a long way to go,researchers are still constantly developing more excellent COF,and strive to give full play to the advantages of COF in biomedicine,the application of COF can be expected in the future.