Functional Design And Application Of Composite Nanomaterials Based On Transition Metals For Photothermal Therapy And Radiosensitization

Tumor is one of the main diseases leading to human death.In order to treat cancer,scientists have developed chemotherapy,radiotherapy,surgical resection and other treatments.However,due to the metastasis and invasiveness of tumor and the immunosuppression of tumor microenvironment,the therapeutic effect of these methods is not always satisfactory.Photothermal therapy has the advantages of less trauma and low side effects.The development of photothermal reagents with high photothermal conversion efficiency,good s tabilit y,low toxicit y and clear action mechanism is the current research hotspot.In addition,the hypoxia of tumor microenvironment limits the effect of radiotherapy and the damage of high dose radiation to normal tissue.Therefore,there is an urgent ne ed to design and synthesize radiotherapy sensitizers to alleviate tumor hypoxia,improve the efficacy of radiotherapy and reduce the damage to normal radiation tissue.In this thesis,we designed two kinds of composite nanomaterials based on transition met al elements,and explored the imaging-guided photothermal anti-tumor and its mechanism,and studied as a radiosensitizer to improve the effect of radiotherapy and enhance the resistance of normal cells to radiation.The current research results are as follows:1.Designing highly stable black-ferrous selenide phosphorus nanosheets heteronanostructure for MRI-guided photothermal therapy.It is an urgent problem to design photothermal reagents with stable,non-cumulative toxicity,high photothermal conversion efficiency and clear mechanism to achieve accurate photothermal therapy guided by imaging.In this paper,we successfully designed monodisperse superparamagnetic ferrous selenide（FeSe₂）and black phosphorus nano-sheet（BPs）to form BPs-FeSe₂,by P-Se bond and modified heterojunction nanoparticles with methoxy polyethylene glycol amino（m PEG-NH₂）.Good water solubility was obtained and used in photothermal tumor therapy guided by MR imaging.The improvement of photothermal conversion efficiency of BPs-FeSe₂-PEG by BPs-FeSe₂-PEG is due to the effective separation of photogenerated carriers caused by the formation of heterojunctions.In addition,through the formation of P-Se bond,the oxidation degree of FeSe₂ is weakened,and the lone pair electrons on the surface of BPs are occupied,which reduces the exposure of lone pair electrons in the air,so that BPs-FeSe₂-PEG has good stability.In addition,the aggregation of FeSe₂ on the surface of BPs and the modification of m PEG-NH₂ lead to the formation of hydrogen bonds,which enables BPs-FeSe₂-PEG to enhance the effect of T₂-weighted imaging,thus providing accurate image guidance for the process of photothermal therapy.BPs-FeSe₂-PEG generates enough heat to inhibit tumor growth under near-infrared laser irradiation and gradually degrades in vivo.2.Oxygen-supplementing CeO₂-MnO₂ nanoparticles for radiotherapy of hypoxic cancer.Radiotherapy is affected by hypoxia in tumor microenvironment,which leads to poor effect of radiotherapy.Therefore,it is urgent to alleviate the hypoxia state of tumor in order to improve the effect of radiotherapy.We have designed and synthesized nanocomposites with CeO₂ short rods as the core and coated with MnO₂.The nanomaterial has the dual response characteristics of H₂O₂and GSH,which can catalyze the overexpression of H₂O₂ in the tumor to produceO₂ to alleviate hypoxia,and CeO₂ have a certain radiation protective effect on normal cells.The characterization shows that CeO₂-MnO₂ is a rod-like nanomaterial with a length of about 100 nm.The catalytic experiment in vitro shows that CeO₂-MnO₂-PEG has a good effect of oxygen production and GSH consumption.In vitro experiments showed that CeO₂-MnO₂-PEG could reduce the killing effect of radiation on normal cells.In vitro and in vivo experiments show that CeO₂-MnO₂-PEG combined with X-ray can effectively inhibit tumor growth.Taken together,based on the transition metal elements,we synthesized BPs-FeSe₂-PEG and CeO₂-MnO₂-PEG nanocomposites as photothermal reagents and radiosensitizers respectively,which provide a scientific basis for the further development of multifunctional nanocomposites.