Design And Constrution Of Multifunctional Coreshell Nanotherapy System And Its Application In Multimodal Treatment Of Tumor

With the rapid development of nanotechnology,nanomedicine has made great progress in tumor treatment.The delivery of nanomaterials requires two main types of chemical impulses:active delivery and passive delivery.However,no matter which delivery mode,the goal is to achieve efficient inhibition of tumor cells and thus achieve tumor tissue apoptosis.The microenvironment at the tumor site is characterized by slight acidity,high concentration of glutathione,poor heat resistance,and the need for a large amount of glucose as its own energy substance to achieve rampant reproduction.According to these characteristics,the following four types of multifunctional collaborative tumor nanosystems are designed:1.According to the cell fluid at the tumor tissue is slightly acidic（≈5.4）,and the tumor cell fluid contains a high concentration of reducing peptide glutathione（GSH）,and the tumor cells will be occurred thermal ablation when the temperature>42℃,so a two-mode diagnosis and treatment system（HPDA/5-Fu@Mn O₂）was designed.The system is composed of hollow polydopamine（HPDA）loaded with a broad spectrum of chemotherapeutic drug 5-fluorouracil（5-Fu）,and finally coated with manganese dioxide（Mn O₂）.When the nanoagent is irradiated with a laser,intense photothermal reactions occur between the outer Mn O₂ shell and the inner hollow PDA nucleus,releasing heat to ablate tumor cells.At the same time,the loaded chemotherapeutic drug 5-Fu was released with the rupture of hollow PDA shell,which made photothermal therapy and chemotherapy synchronized.Not only does the coated Mn O₂ act as a gatekeeper,but the flower-like shell of Mn O₂ reacts efficiently with glutathione at the tumor site to facilitate the release of the internally loaded chemotherapeutic drugs.The photothermal performance of the nano medicinal agent was measured.The photothermal conversion efficiency of it was calculated to be34.4%.The sustained release test also showed that the nano treatment agent had significant microacid response.At the same time,cytotoxicity experiments proved that the treatment agent could play a synergistic treatment mode of combining chemotherapy and photothermal therapy under laser irradiation,and the death rate of Hela cells was up to 80.91%.These results also prove that the nanoparticles are an ideal class of tumor inhibitors.2.Based on the mild acid and not adopt to higher heat in cancer microenvironment,designed acid-responsed a nanocomposites Cu₂O@Au@PDA/5-Fu@Ca CO₃,which can give play to photothermal therapy and chemical therapy.The nanocomposite in this chapter firstly synthesized cuprous oxide（Cu₂O）nanospheres by the reaction of high concentration ascorbic acid and Cu SO₄·5H₂O,and then dropped chlorauric acid into the Cu₂O which was stirred at high speed to uniformly load Au nanoparticles on its surface and then synthesized Cu₂O@Au nanospheres.Next coated a layer PDA membrane through adjust the solution p H,the surface of PDA possesses abundant chemical bond,which can be bonded with 5-Fu,finally cladding a layer calcium carbonate（Ca CO₃）that can be packed with the inner core.Used the drug capture rate,drug sustained release,photothermal performance and MTS toxicity experiments to further prove the performance of nanocomposites Cu₂O@Au@PDA/5-Fu@Ca CO₃.The results show that it possesses higher drug releasing rate in the simulate cancer microenvironment（ΔY=0.2885）,unbelievable photothermal conversion ability（33.9%）,and in the final cytotoxicity test,better tumor cell killing effect was also observed under multi-mode collaborative therapy（81.82%）.3.Given the slightly acidic environment of the tumor tissue and its inability to tolerate high heat,designed a photothermal therapy and chemical therapy double responded nanocomposites m PB@PEI/Ag₂S/5-Fu@PDA,whose carrier is mesoporous Prussian blue（m PB）,meanwhile,need acid and NIR trigger it to come into play.The nanocarriers have mesoporous sphere prussian blue（PB）,whose mesoporous construction can provide a great number of active site,which can connect with drug molecule a lot,more importantly,amino of m PB can absorb a lot of silver sulphide（Ag₂S）QDs,further increase their photothermal performance to achieve the aim of thermal ablation.More importantly,5-Fu can further improve its therapeutic effect.A series of performance experiments results indicate it has higher drug loading rate（25.37%）,faster drug releasing rate（ΔY=0.2012）,outstanding photothermal conversion rate（32.4%）,and synergistic treatment larger fatality rate（82.54%）.4.According to the peculiarities of cancer:mild acid microenvironment,highconcentration glutathione,and of great necessity of a great amount of glucose to consume to meet its requirement,designed a nanoparticle that contains higher photothermal conversion rate-Au nanostars,coated mesoporous Si O₂,at the same time,loaded 5-Fu and glucose oxidase（GOD）.This chapter uses typical soft template,obtained the nanocore of Au@m Si O₂,where connected a great number of amino,it can provide many active sites,to absorb 5-Fu and enzymes.Finally,we coated PDA membrane to get the nanocomposites Au@m Si O₂/5-Fu/GOD@PDA.A diversity of performance experiments dedicates that it has higher drug loading rate（27.98%）,and faster drug releasing rate compares than the rate of formal body fluid（ΔY=0.3398）,meanwhile,larger photothermal conversion rating（35.2%）,more importantly,effective anti-cancer performance（82.35%）,to achieve excellent cure effects.