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Fabrication And Application Of Multifunctional Therapeutic Nanosystem

Posted on:2019-03-11Degree:DoctorType:Dissertation
Country:ChinaCandidate:T T ZhangFull Text:PDF
GTID:1361330572452671Subject:Analytical Chemistry
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Nanomedicine is the biomedical application of nanoscale materials for diagnosis and therapy of cancer,which significantly overcome these issues existed in traditional treatment,such as poor targeting and poor tissue penetration,therapeutic effects and side effects.Rencently,nanomaterials,with large specific surface area,small size,good biocompatibility and easy multifunctional modification,have been widely applied in optical imaging,MRI,photoacoustic imaging,drug delivery and photothermal therapy of tumor.Then,designing multifunctional theranostic nanosystem with simultaneous imaging and therapy would be significant for precise cancer treatment.In this system,we focus on the development of multifunctional integrated nanotherapeutic systems based on the light,magnetic and thermal properties of nanomaterials,which successfully achieved cancer cell specific target recognition,drug controlled release and multi-mode imaging monitoring.1.A multifunctional silver nanocomposite for the apoptosis of cancer cells andintracellular imagingWe constructed a novel therapeutic nanosystem with the combination of good biocompatible,stable silica nanomaterials and small size silver nanoparticles,which can identify cancer cells with specific targeting,trace the cell and induce cancer cell apoptosis.Compared with traditional therapy methods,this method avoids the use of anticancer drugs and greatly reduces the side effects in the treatment of cancer.Based on the SiO2@Ag-PEG/RGD/NLS complex,it can target cancer cells and induce apoptosis of cancer cells and this method provides a new way for the treatment of cancer.2.Hyrogen Peroxide-Responsive Cancer TherapyWe constructed a drug delivery and release nanosystem based on intracellular redox reaction.Based on the principle of Fenton reaction,we use the excessive hydrogen peroxide in cancer cells to produce hydroxyl radical,which can control the release of drugs and reduce the side effects of unexpected release of drugs in normal tissues.In addition,the hydroxyl radical produced by the Fenton reaction can destroy the respiratory chain to stimulate the release of cytochrome C,activate the apoptosis pathway and induce cancer cell apoptosis.Both anticancer drugs and hydroxyl radical can effectively improve the therapeutic effect and provide a new idea for cancer enhanced therapy.3.Redox-Activated Theranostic Nanoagent:Toward Multi-Mode Imaging Guided Chemo-Photothermal TherapyHypoxia is one of the major characteristics of solid tumors,which limits the therapeutic effect of chemotherapy and radiotherapy.The development of multi-functional integrated nanotherapeutic agents is of great significance for the treatment of hypoxic tumors.Based on this,we designed and synthesized a multi-mode image-guided chemo/photothermal therapy nanotherapeutic reagent,which could be monitored by fluorescence imaging and magnetic resonance imaging.At the same time,this reagent can also achieve photothermal/chemotherapeutic synergistic treatment of hypoxic solid tumor.Under the irradiation of near-infrared light,the photothermal properties of gold shell nanomaterials can increase the temperature and increase the blood flow,thus regulating the anoxia of tumor microenvironment.The intelligent nano-complex SiO2@Au@MnO2-DOX/Apt was injected into the tumor-bearing mice via tail vein.The nano-therapy reagent accumulated in the tumor site and showed a strong photothermal/chemotherapeutic synergistic effect.Our nanotherapy system has great potential for hypoxic tumor therapy.
Keywords/Search Tags:Silver nanoparticle, nanocomposite, cell apoptosis, reactive oxygen species, cell imaging, mesoporous silica nanoparticles, hydrogen peroxide, controlled drug release, hydroxyl radical, enhanced therapy, core-shell nanoparticle, tumor hypoxemia
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