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Preparation Of Theranostic Nanosystem For The Diagnosis And Treatment Of Tumor

Posted on:2022-11-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:J M XiaoFull Text:PDF
GTID:1521306323462604Subject:Materials Physics and Chemistry
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Nowadays,the number of cancer(malignant tumor)patients has risen significantly,and the symptom of cancer patient isn’t obvious in the long incubation period,which can significantly enhance the fatality rate of cancer patients.Therefore,it is very critical to develop the early diagnosis and treatment of tumors for decreasing the fatality rate of patients.In decade,the rapid development of nanotechnology in medical field will bring dawn for the precise diagnosis and efficient treatment of malignant tumors.Nanomagnetic material has been widely explored to serve as magnetic resonance contrast agents(MRCAs)for improving the resolution ratio of tumor tissues in magnetic resonance imaging,which can obviously improve the accurate diagnosis for tumors.Meanwhile,this nanoparticles with suitable diameter can enter cancer cells,and it further enhance the concentration of MRCAs in tumor tissues and further improve the accurate diagnosis of tumor.In addition the free anticancer drug entered tumor tissues mainly depends on the intravenous injection and oral administration.However,the concentration of anticancer drug arrived in tumor tissues is low due to the complexity of human structure,and the anticancer drug randomly enters normal tissues and further lead to the generation of side effect.To improve the therapeutic efficacy of tumors,the nanoparticles with excellent biosafety can serve as drug carriers for the targeting delivery of drugs,and further cause the content of drugs in tumor tissues increasing,which is beneficial to achieve efficient treatment for tumor.Meanwhile,the drug carriers can simultaneously avoid the generation of side effect for body.The nanoparticles with high biocompatibility were utilized to building the diagnostic nanoplatform and therapeutic nanoplatform in this paper.This nanoplatform can simultaneously achieve the diagnosis and treatment ability,and further improve the accuracy of diagnosis and treatment effect.Therefore,this nanoplatform opens a whole novel set of opportunities for nanomedicine and biomedical engineering research.This paper mainly includes the following parts:1.MRI technology is frequently employed for the accurate diagnosis of cancer patients in clinic.In generally,the MRCAs are widely utilized to enhance the accuracy of diagnosis due to the complexity of tissue structure.It is noteworthy that the magnetic iron oxide nanoparticles can enhance the contrast between normal tissues and tumor tissues,so this nanoparticles can serve as MRCAs.However,the factors that affect the T2 relaxation signal of monodispersed nanomagnetic iron oxide nanoclusters(NMIONC)are still not clear.Therefore,the different types of NMIONCs were synthesized to investigate the contrast ability of influence factors.Subsequently,the MR contrast ability of NMIONCs was further demonstrated by the mice experiment.Therefore,this work opened a novel way for fabricating the MRCAs with high MR contrast property.2.The nanoparticles as drug delivery systems are widely developed in cancer field due to its high biocompatibility and loading capacity,and it can obviously enhance the therapeutic efficacy of tumor.In this paper,we utilized the pseudomonas geniculate to act as the source of cell membrane and further synthesize the self-assembly biomimetic cytomembrane-based nanoplatform.Subsequently,the free Mn2+ ions,selenium(Se)nanoparticles,and anticancer drug(doxorubicin,DOX)were further loaded in this nanoplatform for synthesizing the cytomembrane-based synergistic therapy nanoplatform.This nanoplatform showed the high internalization efficiency of cancer cells,which was beneficial to the delivery of anticancer drug and futher enhance the therapeutic efficacy of tumor.Furthermore,this nanoplatform could promote the generation of reactive oxygen species(ROS)in cancer cells via activating the superoxide dismutase-1(SOD-1)expression,which was beneficial to realize the synergistic therapy of tumors.Therefore,this work widened a novel view for the application of self-assembly biomimetic cytomembrane-based nanoplatform in tumor field.3.In recent decade,chemodynamic therapy(CDT)has gradually become the research focus in cancer field.However,the amount of ROS in vivo is finite,and it significantly hind the application of CDT in clinic.Therefore,the manganese carbonate-deposited iron oxide nanoparticles were synthesized,and this nanoparticles with high longitudinal relaxivity value were employed to load Se nanoparticles for constructing the theranostics nanoplatform.This nanoplatform could release the massive Mn2+ions in the tumor microenvironment,and free Mn2+ ions could act as MRCAs.In addition,the free Mn2+ ions and Se nanoparticles could synergistically enhance the concentration of ROS,and simultaneously inhibit the generation of adenosine triphosphate(ATP)in cancer cells.Therefore,this theranostic nanoplatform could replace the chemotherapy and simultaneously realize the diagnosis and treatment of tumors.
Keywords/Search Tags:magnetic resonance contrast agents, nanomagnetic iron oxide nanoclusters, cell membrane, chemodynamic therapy, theranostic nanoplatform
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