Donor-Acceptor COF And Its Derivative For Photothermal Treatment Of Breast Cancer

Breast cancer is one of the most common malignant tumors in women,with the incidence ranking first among all malignant tumors in the female body in China.Currently,the most commonly used clinical treatment modalities are surgery,radiotherapy and chemotherapy or combination therapy.Although these treatments can inhibit tumor growth to a certain extent,they also have their own inherent disadvantages,such as side effects.With the development of science and technology,many new cancer treatment modalities such as photothermal therapy,photodynamic therapy,immunotherapy and chemodynamic therapy have emerged.Photothermal therapy is a minimally invasive treatment method with a good prospect of application in the field of cancer treatment.Although photothermal therapy avoids organ damage to a certain extent,some photothermal reagents have low photothermal conversion efficiency and require high power laser excitation to reach the appropriate temperature to ablate the tumor when applied.Therefore,the development of new materials with high photothermal conversion efficiency to improve the disadvantages of photothermal therapy has become a hot topic of research nowadays.In recent years,researchers have developed Covalent Organic Frameworks(COFs)based on Metal Organic Frameworks(MOFs).COFs are crystalline porous materials constructed from organic molecules with an atomically precise and ordered structure,which also has the advantage of being structurally tunable.Compared to MOFs,COFs do not contain metal elements in their structure,thus avoiding the toxicity caused by the excessive use of heavy metals and providing a higher level of biosafety.Therefore,it is promising to use the structural advantages of COFs to construct efficient photothermal reagents for cancer therapy.In this thesis,covalent organic framework material and its derivative were synthesized and used in the photothermal treatment of breast cancer.1.A donor-acceptor covalent organic framework(COF),TB-COF,constructed from an electron-rich building unit(donor)and an electron-deficient building unit(acceptor),was developed as a promising photothermal agent for photothermal therapy(PTT).Upon laser irradiation,significant photoinduced electron transfer(PET)occurs between the donor and acceptor in TB-COF,converting the absorbed optical energy to thermal energy and resulting in the ablation of tumor.TB-COF possessed satisfying photothermal conversion efficiency,reaching43.65%,similar to materials commonly used for PTT.Moreover,hyaluronic acid(HA)was coated on TB-COF to improve its biocompatibility and achieve tumor targeting.Furthermore,in vitro and in vivo experiments confirmed satisfying photothermal anticancer efficacy of TB-COF-HA.2.A covalent organic framework(COF)derived “all-in-one” carbon-based nanozyme was devised to achieve synergistic enhanced catalytic therapy and NIR-II photothermal therapy of cancer.Originated from the intrinsic property of carbon-based materials,the nanozyme showed excellent photothermal activity towards cancer cell killing upon NIR-II laser irradiation.Furthermore,the developed nanozyme possessed three enzyme-like activities,including oxidase(OXD)-like activity,catalase(CAT)-like,and peroxidase(POD)-like catalytic activity,which enabled the nanozyme to produce adequate reactive oxygen species(ROS)to kill cancer cells.It could also improve the catalytic effect by exerting CAT-like activity that can also improve the lack of oxygen at the tumor.Compared to biological enzymes,the nanoenzyme maintained efficient catalytic performance even in the slightly acidic environment.In vitro and in vivo studies demonstrated this ’all-in-one’ nanoenzyme could synergistically enhance the effects of catalytic therapy and NIR-II photothermal therapy to achieve efficient tumor ablation.