The Heterogeneous Nanocrystals For Radiosensitization Enhanced Therapy Of Cancer

Radiotherapy(RT)is one of the most important and effective methods for the treatment of solid tumors.More than half of tumor patients would receive RT during treatment.It has a variety of advantages such as no limit to the tissue penetration depth.However,there is small difference between tumor and normal tissues in their responses to ionizing radiation.So,it is difficult to successfully cure solid tumors without damage to normal tissues with the used dose and frequency.Therefore,it is highly significant to improve the radio sensitivity of tumor to enhance the effect of radiotherapy and reduce the side effects of radiation.With the development of nanomedicine,various nanoparticles have been used in radiotherapy to improve the radio sensitivity of tumor,as they have various advantages of multifunctions,easy modification,and good biocompatibility.They can be enriched at tumor site via the enhanced permeability and retention effect(EPR).The nanoparticles containing the high atomic number(high-Z)elements especially Au-based nanoparticles have attracted considerable attention due to their multifunction.The high-Z nanoparticles can not only increase the amount of X-ray deposited into tumor and improve the lethality of radiation to tumor cells,but also synergize with other functions(such as photothermal properties)to further enhance the therapeutic effect of the tumor.In this thesis,the dumbbell-shaped heterogeneous copper selenide-gold nanocrystals were synthesized by spontaneous redox reactions between Cu2-xSe and Au3+ without other reducing agents in the water phase at room temperature.Both of the X-ray attenuation and photothermal conversion efficiency of the dumbbell-shaped heterogeneous copper selenide-gold nanocrystals were improved through the synergistic effect of Cu2-xSe and Au.The copper selenide-gold nanocrystals were modified with thiol-functionalized polyethylene glycol to make them lower cytotoxicity,better biocompatibility,and longer blood circulation time,all of which are good for improving their accumulation at tumor site to ensure better performance in imaging and treatment.The improved photothermal conversion efficiency and X-ray attenuation coefficient of copper selenide-gold nanocrystals ensures them as a multimodality imaging contrast agent(such as photoacoustic imaging,CT imaging,and SPECT imaging)and an image-guided radiosensitizer in synergistic radio-photothermal therapy for cancer.In addition,this study provides a new idea for enhancing diagnosis and treatment effect of tumor by the formation of heterostructure nanomaterials from high-Z elements and low atomic number elements.