Preparation Of Hollow Mesoporous Ferrite Magnetic Nanocomposite And Its Multi-mode Combined Anti-tumor Research

Cancer is the main cause of harm to human life and an important obstacle to increasing life expectancy.In recent years,with the gradual deepening of tumor research,a specific treatment method developed for the tumor microenvironment——Chemodynamic Therapy（CDT）has attracted much attention.Chemodynamic therapy based on traditional Fenton reaction was that iron-containing nanomaterials dissolved ferrous ions in a slightly acidic tumor microenvironment.Ferrous ions reacted with H₂O₂ over-expressed in the tumor site to produce·OH,which made cancer cells apoptosis due to lipid peroxidation.Due to the special conditions for the occurrence of Fenton reaction,the weakly alkaline environment in normal cells and the low content of H₂O₂ greatly reduced its toxicity to normal tissues.This specific treatment strategy has the potential for clinical transformation.However,chemodynamic therapy based on the traditional Fenton reaction was still ineffective due to the low reaction rate in the tumor and the depletion of reducing substances（GSH）.Combining chemodynamic therapy with other treatment methods for combination therapy is an effective strategy to improve efficacy.This thesis designed and synthesized spinel ferrite nanoparticles with hollow mesoporous structure,and constructed two new types of composite nanocarriers based on this,which could improve the therapeutic effect of tumors by integrating a variety of treatment methods.The specific work is as follows:1.The non-ionic surfactant Pluronic F-127 with high biological safety was used as a template to prepare hollow mesoporous copper ferrite（H-Cu Fe₂O₄）nanoparticles by solvothermal method,and explored the effect of reaction time and the content of F-127 and Na Ac on the size and morphology of H-Cu Fe₂O₄.The results showed that the optimal conditions for preparing H-Cu Fe₂O₄ particles were as follows:temperature was 200℃,F-127content was 1.0 g,Na Ac dosage was 15 mmol,and reaction time was 16 h.The H-Cu Fe₂O₄obtained under these conditions has been an average particle size of 275 nm and a shell thickness of 80 nm.It has been a suitable specific surface area（33.013 m²/g）and pore size（3.5nm）,which can be used for the loading of small molecule drugs.The higher saturation magnetization（31.13 emu/g）can be used for magnetic targeting.This nanoparticle is expected to serve as a magnetically targeted drug carrier.2.The curcumin was used as a model drug for loading,and the results showed that the drug loading rate of H-Cu Fe₂O₄ was close to 40%.Then it was modified by surface polymerization of dopamine to enhance its hydrophilicity and biocompatibility,thereby constructing the H-Cu Fe₂O₄@Cur@PDA nanosystem.Among them,H-Cu Fe₂O₄ can effectively consume the reducing substance glutathione and release Cu⁺/Fe²⁺to promote the CDT effect.At the same time,the good light-to-heat conversion efficiency of polydopamine（32.25%）can increase the temperature of the system and further promote the CDT effect.This design has realized the synergy of CDT,chemotherapy and photothermal therapy,and the inhibition rate of tumor cells reached 85%,shown good anti-tumor potential.3.The self-enhanced H-Mn Fe₂O₄@PDA-GOx nano-Fenton preparation was further designed and constructed,GOx was grafted onto the surface of H-Mn Fe₂O₄@PDA through amide bond,and then the sequential catalytic reaction in the cell was used to effectively kill the tumor.When H-Mn Fe₂O₄@PDA-GOx entered the cell,H-Mn Fe₂O₄would first catalyze H₂O₂to produce O₂ and created conditions for GOx to decompose glucose.After further accumulation of gluconic acid,the intracellular p H decreased,then Fe³⁺/Mn²⁺would react with H₂O₂ to produce·OH to kill tumor cells.In addition,exogenous near-infrared light increaseed the temperature inside the cell,which would further promote the occurrence of the above sequential catalytic reactions.This composite nanomaterial organically has combined starvation therapy,photothermal therapy and chemodynamic therapy to achieve a good anti-tumor effect.