Font Size: a A A

Multifunctional Nano-ruthenium Drug Delivery System Combined With Chemotherapy & Photothermal-Photodynamic Therapy For Glioma

Posted on:2020-04-12Degree:MasterType:Thesis
Country:ChinaCandidate:X F ZhuFull Text:PDF
GTID:2404330620452424Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
Gliomas are the most invasive intracranial brain tumors with a very poor prognosis,a high recurrence tendency,and a low five-year survival rate.Gliomas are the most invasive intracranial brain tumors with very poor prognosis,high recurrence tendency,and low five-year survival rate.At present,the treatment of glioma mainly includes surgery,radiotherapy and chemotherapy.However,due to the complexity of the intracranial nerve structure and the invasive growth of glioma,the treatment effect is poor and the side effects are high.In recent years,the development and application of drug delivery systems have attracted widespread attention and have great clinical therapeutic potential.However,the study found that the delivery nanosystem can only transport very small amount of drugs to the tumor site,which seriously hinders the application of the delivery nanosystem.Therefore,it is necessary to rationally design and construct drug delivery system that enhances the targeting and tumor enrichment ability.In addition,the single mathod of treatmment glioma is not effective,and increasing the treatment cycle brings more discomfort to the patient.Recently,with the development of cancer treatment methods and the rapid development of nanotechnology.Compared with the single treatment mode,the multi-modal treatment synergistic showed super-additive effect of 1+1>2,which greatly improved the therapeutic effect of cancer and prolonged the survival period.As a new type of tumor treatment model,optical therapy can achieve remote control and improve the safety of normal tissues in the body.The targeted chemotherapy mode has high enrichment and low tissue toxic side effects.If optical therapy and targeted chemotherapy can be combined to construct a light-regulated targeted chemotherapy model,this will bring new ideas and strategies for glioma treatment.Based on the above research background,a series of drug delivery systems were rationally designed and synthesized for the combined treatment of glioma,aiming to develop a new glioma light-regulating nano drug delivery system with in vivo tracing and high-efficiency treatment.The role of reducing the toxicity of traditional drugs and improving the therapeutic effect of glioma,to achieve a new strategy for synergistic treatment of glioma,the full text is divided into three chapters.In chapter 1 is the introduction part,briefly introduces the research progress of inorganic metal nanocarriers in biomedicine and the research progress of drug delivery system in the treatment of glioma,focusing on the optical therapy and targeted chemotherapy in the brain.In chapter 2,we have developed a mesoporous nanosystem with redox control and dual targeting using a template approach to enhance the therapeutic potential of gliomas.Unlike traditional nanoparticles,which are based on the passive targeting of targeted tumor site accumulation,are known as enhanced permeability and retention effects.RBT@MRN-SS-Tf/Apt,the active targeting of receptors and ligands not only overcomes the blood-brain barrier,but also actively targets gliomas.At the same time,disulfidemediated redox-responsive release of drugs has enabled ondemand drug delivery strategies.In addition,due to the loading of RBT,RBT@MRN-SS-Tf/Apt produces reactive oxygen species under 808 nm laser irradiation,thereby inducing apoptosis of tumor cells,which provides photodynamic therapy for gliomas.On the one hand,RBT@MRN-SS-Tf/Apt has a significant inhibitory effect on U87 3D tumor cell spheres.On the other hand,RBT@MRN-SS-Tf/Apt can penetrate deeply into 3D tumor cell spheres.These results indicate RBT@MRN-SS-Tf/Apt may be able to adapt to the invasive growth pattern of glioma and greatly improve the therapeutic effect.In the tumor-bearing nude mouse model,we used RBT as a fluorescent probe to observe the tissue distribution and specific brain targeting of RBT@MRN-SS-Tf/Apt.After treatment with RBT@MRN-SS-Tf/Apt,the median survival of nude mice was prolonged,but in the RBT@MRN-SS-Tf/Apt combined with PDT treatment group,indicating the potential application value and the ideal therapeutic effect of combination therapy.This study,combined with photodynamic therapy,provides new ideas and insights for the design of dual-targeted nano drug delivery systems,and photodynamic therapy is expected to be applied to other cancer drug delivery systems.In chapter 3,In the third chapter,the MnO2-modified erythrocyte membrane nano-drug drug delivery platform?RBCm@Ru-MnO2?was synthesized by biomineralization of cell membrane,and the combination of chemotherapy/photothermal-photodynamic therapy for glioma was realized.First,RBCm@Ru-MnO2@DOX showed a potent EPR tumor accumulation effect after tail vein administration.Once in the tumor,MnO2 in RBCm@Ru-MnO2@DOX will react with the endogenous H2O2 of the tumor microenvironment to produce oxygen and reduce hypoxia in solid tumors,thereby overcoming the hypoxia-related photodynamic resistance during PDT cancer treatment.At the same time,the reaction of MnO2 with H+and H2O2 in the tumor microenvironment will result in the gradual release of DOX from these erythrocyte membrane-MnO2 nanoparticles to achieve significantly improved intratumoral interstitial spread for optimal tumor treatment.In vitro experiments showed that RBCm@Ru-MnO2@DOX has good stability,immune evasion ability and tumor permeability.In vivo experiments showed excellent tumor enrichment effects as well as synergistic anti-tumor effects.In addition,in vitro and in vivo experiments have shown that RBCm@Ru-MnO2@DOX has pH/H2O2responsiveness for chemotherapy/photothermal-photodynamic combination therapy for glioma.This study shows that this catalytically active biomimetic nanosystem can be used as an effective and powerful combination therapy system for the treatment of tumors,and is promising for future clinical cancer treatment.
Keywords/Search Tags:glioma, targeted chemotherapy, photodynamic therapy, photothermal therapy, combination therapy
PDF Full Text Request
Related items