Organic Photothermal Agent For Enhanced Photothermal Therapy

Cancer,commonly known as malignant tumors,is listed by the World Health Organization(WHO)as one of the five major incurable diseases in the world,and it has become the most terrible "killer" threatening human health.Normal cells are induced by carcinogenic factors such as physics,chemistry,and viruses,causing mutations in protooncogenes and tumor suppressor genes to form cancer.Compared with normal cells,cancer cells have the characteristics of unlimited proliferation,transformability and easy transfer,which also causes damage to normal tissue cells,making it difficult to be cured.In recent years,with the improvement of human living standards,the diet has become more diversified,which has also led to an increase in the incidence of malignant tumors.According to national cancer statistics which released by the National Cancer Center,the number of new cases is 3.8 million,and an average of more than 10,000 people are diagnosed with cancer every day.Therefore,how to treat cancer efficiently and safely has become an important problem facing today's society.At present,the treatments for tumor generally includes chemotherapy,radiotherapy,immunotherapy and photodynamic therapy.However,there are some defects in these treatments that limit their practical application,such as chemotherapy and radiotherapy have a long cycle and a large damage to normal tissue cells,which can cause additional toxic side effects on the body.Besides,simple immunotherapy can not completely eradicate tumor cells,and it is used in combination with other treatments for adjuvant treatment.As a new type of treatment,photodynamic therapy has certain novelty,but its inherent defects in the tumor environment-hypoxia,which cause some problems in photodynamic therapy.As another new treatment method,photothermal therapy has attracted the attention of a large number of scholars in recent years.The advantages of photothermal therapy are high selectivity,non-invasiveness,and repeatable treatment.Therefore,the development of new photothermal materials to achieve efficient killing for tumor tissue has become a hot topic in this field.In recent years,many inorganic nanomaterials,including gold nanorods,carbon nanotubes,metal oxides,metal sulfides,graphenes,and black phosphorus nanosheets,have been widely used for photothermal therapy for cancer in the near-infrared region.In particular,functional inorganic nanoparticles,such as targeting and drug delivery functions,can increase the selectivity and therapeutic efficacy of photothermal therapy.However,inorganic nanomaterials themselves have defects such as poor biodegradability,potential toxicity,and difficulty in reproducibility,which limit clinical applications in the future.Therefore,developing a photothermal reagent(with high selectivity,low toxicity,and good reproducibility)has become an urgent problem to be solved.This thesis designs and synthesizes a series type of photothermal reagents,which has good photothermal conversion efficiency.By simple modification of organic photothermal reagent,it has better property that can achieve a better therapeutic effect on the tumor.Specific experiments include the following two aspects: 1.A novel photothermal reagent with dual targeting function was designed and synthesized.The photothermal reagent is based on cyanine-like,and linked to the corresponding functional biotin which target tumor cell membrane receptor protein and triphenylphosphine targeting mitochondria.Therefore,organic small molecule photothermal reagents achieve dual targeting of tumors.The photothermal reagent not only has better photothermal conversion efficiency,but also has a good therapeutic effect on tumors.And it has the effects of fluorescence imaging and photoacoustic imaging,so that it can be applied to the integration of diagnosis and treatment of tumors,and photothermal treatment in the future.This photothermal treatment provides a new platform for clinical application.2.We design and synthesize a kind of organic photothermal reagent with anti-inflammatory function.The photothermal reagent uses the cyanine-like structure as the main structure and modifies the tumor targeting cyclic peptide cRGD to realize the active targeting of tumor cells,and anti-inflammatory small molecule drugs to achieve anti-inflammatory effects on tumor treatment.The photothermal reagent can not only form micelles by self-assembly,but also enhances its water solubility and enhances its circulation in the body.Moreover,by utilizing the acidic condition of the tumor microenvironment,it can break the ester bond in the small molecule and achieve an anti-inflammatory effect on the tumor.This organic photothermal reagent has a better therapeutic effect on tumors,and also provides a new idea for the design of cancer therapeutic drugs.