The Design,Synthesis,and Biological Applications Of Cancer Cell Membrane Coated Manganese Dioxide Nanoreactors

Cancer,also known as malignant tumor,is a cell with abnormal biological characteristics that is formed by mutation of normal cells under some abnormal conditions,and then develops into tumor tissue,which is a fatal disease that seriously threatens human health.In recent years,the incidence of cancer has increased year by year,and has developed into the number one killer of human beings.How to effectively cure cancer is a major problem in the medical field at this stage.More and more people are struggling to treat cancer.Photodynamic therapy(PDT)is an emerging cancer treatment method.The principle is that the drug photosensitizer produces energy from specific wavelengths and transmits it to surrounding molecules.Toxic substances such as reactive oxygen species kill cancer cells for the purpose of treating cancer.PDT has many unique advantages,such as low systemic toxicity,lack of initial resistance,and no invasive behavior.It is precisely because of these advantages that PDT has become a very promising cancer treatment method.Radiotherapy is also existing clinically mature treatment plan and it is to use the high-energy radiation such as X-rays and electron lines to directly kill cancer cells or generate active oxygen to kill cancer cells indirectly,thereby achieving the purpose of treating cancer.These treatments have had a profound impact on cancer therapy and have made a tremendous contribution to human health.Photodynamic therapy and radiation therapy kill tumor cells by reacting with oxygen molecules in the tumor site to produce reactive oxygen species.It is well known that the tumor site is hypoxic,and therefore it will largely affect photodynamic therapy and radiation therapy.More and more people are working to improve the hypoxic environment of the tumor site to enhance the therapeutic effect of cancer.Hydrogen peroxide is overexpressed in the tumor microenvironment,and we all know that manganese dioxide can catalyze hydrogen peroxide to produce oxygen.Therefore,the use of manganese dioxide-based nanocomposites to improve the hypoxic environment of tumor sites has been the focus of attention.Manganese dioxide is an important nanomaterial,which has great application prospects in the field of inorganic materials,electrochemical catalysis and biological applications.Especially in biological applications,manganese dioxide can be used as a therapeutic agent in cancer therapy and also can be used as a contrast agent for magnetic imaging in the diagnosis.,Using manganese dioxide nanomaterials for cancer therapy has e a certain degree enhanced the therapeutic effect at present,but the over-expression of hydrogen peroxide in the tumor microenvironment is limited,so the therapeutic effect is not improved.Therefore,how to generate more oxygen in the tumor site to better enhance the therapeutic effect is of great significance.In this work,two kinds of nanomaterials were designed to improve the hypoxic environment of tumor sites based on manganese dioxide,glucose oxidase,photosensitizer Ce6 and radio sensitizer TiO2 and so on,and to be used for photodynamic therapy and radiation therapy.It mainly includes the following two aspects:1.A synergistic treatment of a cancer cell membrane-coated manganese dioxide nanoreactor for photodynamic and starvation therapy was designed.First,hollow mesoporous manganese dioxide nanoparticles(H-MnO2)were prepared,and then glucose oxidase(GOx)was attached to the surface,and photosensitizer Ce6 was placed therein.Finally,the obtained nanocomposite was encapsulated with cancer cell membrane to obtain a nanoparticle H-MnO2-GOx-Ce6@C which has a homologous targeting function.By intravenously injecting nanoparticles into mice,MnO2 converts the endogenous H2O2 into O2 in tumor site,which in turn promotes the conversion of glucose into more H2O2 and in turn produces more O2 in tumor.The nanoparticle transforms the glucose into oxygen at the tumor site through a series of reactions,which cuts off the energy supply to achieve the purpose of starvation treatment,and can generate more active oxygen species under illumination,thereby enhancing the O2-dependent photodynamic therapy.Experiments showed that this combined photodynamic-starvation therapy can significantly kill cancer cells to achieve good therapeutic effects in vivo treatment,and can completely prevent recurrence.2.A cancer cell membrane-coated manganese dioxide nanoreactor was designed and synthesized for the synergistic treatment of radiotherapy combined with starvation therapy.The surface of the radio sensitizer TiO2 was coated with a layer of manganese dioxide,and then glucose oxidase(GOx)was attached to the surface.Finally,the obtained nanocomposite was coated with a cancer cell membrane to obtain TiO2@MnO2-GOx@C that had homologous targeting function.In the presence of manganese dioxide and GOx,the nanoparticle transformed glucose into more oxygen at the tumor site through a series of reactions,which cuts off the energy supply at the tumor tissue and under X-ray irradiation,TiO2 could react with the generated oxygen to generate more reactive oxygen species,which achieves the purpose of combined radiation-starvation therapy and thereby enhanced the effect of cancer radiotherapy.This method has a good application prospect.