| At present,cancer is still one of the main diseases leading to human death.However,traditional treatment methods such as surgery,radiotherapy and chemotherapy not only have high recurrence rate,but also have great limitations and side effects.Therefore,the development of new treatment methods is particularly important.In recent years,phototherapy has been widely studied because of its advantages of less trauma,low dependence and repeatable treatment.Phototherapy can destroy cancer cells by high temperature and reactive oxygen species(ROS),which is including photothermal therapy(PTT)and photodynamic therapy(PDT).Most studies on phototherapy reagents focus on the first near-infrared window(NIRⅠ,700-980 nm),but the low laser penetration depth in this window seriously limits the practical application of phototherapy.Developing reagents suitable for the second near-infrared window(NIRⅡ,1000-1350 nm)can reduce background absorption and scattering and achieve greater penetration depth.Compared with organic materials,inorganic nanomaterials have higher light utilization efficiency and can greatly improve the effect of phototherapy.At the same time,the combination of multiple treatment methods can make up for the deficiency of single treatment method,and is expected to achieve the purpose of radical resection of tumors.Therefore,in this project,two multi-modal therapeutic systems for the second NIR window were prepared based on copper containing compounds.(1)Ce O2/Cu O-PEG-GOD cascade cycle multimodal treatment system was prepared based on nano-copper oxide.GOD oxidizes glucose inside the tumor to starvation treatment by depleting cancer cells of energy materials.At the same time,H2O2 produced in this process can make up for the deficiency of endogenous H2O2 and provide conditions for chemodynamic therapy(CDT)of Cu O.However,Cu O can produce a large amount of ROS during CDT and PDT,which further promotes the production of O2 by Ce O2 and provides conditions for the aerobic oxidation of GOD.The above three processes occur synchronously and promote each other,forming a cascade cycle system.ESR spectra before and after illumination detected characteristic peaks of·OH,·O2-,and 1O2,indicating good CDT and PDT performance of Ce O2/Cu O-PEG.At the same time,GOD also retained good enzymatic activity and could rapidly decompose glucose to produce H2O2.After Ce O2/Cu O-PEG-GOD injection and light irradiation,the survival rate of Hela cells was 12.5%,and the tumor volume of mice treated with the same treatment was much smaller than that of the control group.At the same time,there was no obvious damage to the organs of the mice,indicating that Ce O2/Cu O-PEG-GOD is a safe and efficient composite material.(2)A Cu2Se@m Si O2-PEG-DOX synergistic drug delivery system consisting of PTT,PDT,CDT and chemotherapy was prepared based on copper selenide.Cu2Se exhibited excellent PTT performance,and the tumor temperature rose to 44℃after illumination,with a photothermal conversion efficiency of 33%.ESR spectra before and after illumination revealed that Cu2Se could produce·OH,·O2-and 1O2 by CDT and PDT processes.Cu2Se@m Si O2 has a specific surface area of up to 417.5283 m2/g,and the DOX encapsulation efficiency in Cu2Se@m Si O2 is 65%.The cell survival rate of Cu2Se@m Si O2-PEG-DOX under light conditions was only 8.5%,and the tumor volume of mice treated with the same treatment was extremely small or even disappeared.There was no significant body weight loss and tissue damage in the mice,indicating that Cu2Se@m Si O2-PEG-DOX is a multifunctional treatment system with low toxicity and significant effect. |