【作者】 王超；

【导师】 王凯忠；

【作者基本信息】 吉林大学 ， 临床医学硕士（专业学位）， 2024， 硕士

【摘要】 目的:（1）制备由葡萄糖氧化酶（Glucose oxidase,GOx）和Zn/Cu基双金属离子的金属有机框架（metal-organic frameworks,MOF）共同功能化修饰的聚氨酯（Polyurethane,PU）电纺丝纤维（GOx/BMOFs@PU）,研究GOx/BMOFs@PU纤维的生物相容性及抗肿瘤、抗感染、促愈合特性。方法:（1）GOx/BMOFs@PU的制备及表征:将GOx、Zn⁺、Cu²⁺和2-甲基咪唑通过经典的一锅法反应获得负载GOx的双金属MOF颗粒（GOx/BMOFs）,再将GOx/BMOFs与PU纺丝液共混纺丝,形成GOx/BMOFs@PU。使用扫描电镜（Scanning Electron Microscope,SEM）、透射电镜（Transmission Electron Microscope,TEM）、X-射线衍射（X-Ray Diffractometer,XRD）和傅里叶变换红外光谱仪（Fourier Transform Infrared Spctrometer,FT-IR）分析MOF颗粒及所得纤维的形貌、化学组成和结构。利用纳米粒度及ZETA电位仪分析粒径和电位水平。使用接触角测角仪和电子强力仪测试BMOFs@PU纤维和GOx/BMOFs@PU纤维的亲水性及力学性能。利用电子顺磁共振波谱仪验证羟自由基的产生。（2）GOx/BMOFs@PU的生物相容性评价:采用CCK-8法、浸提液腹腔注射以及小鼠皮下植入实验法评价了所得纤维的生物相容性。（3）GOx/BMOFs@PU的抗菌活性检测:使用菌落计数及抗生物膜实验测试纤维的抗菌特性。（4）GOx/BMOFs@PU的抗肿瘤性能评价:采用CCK-8法、活/死细胞双染色法及荷瘤小鼠体内抗肿瘤实验法评价GOx/BMOFs@PU的抗肿瘤功能。（5）GOx/BMOFs@PU的促愈合评估:采用感染伤口小鼠模型评估GOx/BMOFs@PU的抗感染、促愈合性能。结果:1.构建的GOx/BMOFs@PU纤维具有良好的生物相容性。2.GOx/BMOFs@PU纤维显著抗菌,并对金黄色葡萄球菌生物膜有明显清除能力。3.GOx/BMOFs@PU纤维通过协同饥饿/化学动力疗法,在体外和体内均有效地消除了肿瘤细胞。4.GOx/BMOFs@PU纤维能有效促进感染伤口愈合。结论:GOx/BMOFs@PU复合纤维能够抑制肿瘤复发及促进创口愈合,是肿瘤术后治疗的良好候选材料。更多还原

【Abstract】 Objective（1）Polyurethane（PU）electrospun fibers were prepared by functional modification of Glucose oxidase（GOx）and Zn/Cu based bimetallic organic framework.（2）To investigate the biocompatibility,anti-tumor,anti-infection and pro-healing properties of GOx/BMOFs@PU fiber.Methods In the present study,bimetallic MOF particles loaded with GOx were obtained by the classical one-pot reaction of GOx,Zn⁺,Cu²⁺and2-methylimidazole.GOx/BMOFs@PU was formed by blending GOx/BMOFs with PU spinning solution.The morphology,chemical composition and structure of MOF particles and fibers were analyzed by scanning electron microscopy（SEM）,transmission electron microscopy（TEM）,X-ray diffraction（XRD）and Fourier transform infrared spctrometer（FT-IR）.The particle size and potential level were analyzed by nanometer particle size and ZETA potentiometer.The hydrophilic and mechanical properties of BMOFs@PU and GOx/BMOFs@PU fibers were tested with contact Angle goniometer and electronic strength meter.The generation of hydroxyl radical was verified by electron paramagnetic resonance spectroscopy.The biocompatibility of the obtained fibers was evaluated by CCK-8 method,intraperitoneal injection of extracts and mouse subcutaneous fiber implantation test.The antibacterial properties of the fibers were tested by colony counting and anti-biofilm tests.The antitumor function of GOx/BMOFs@PU was evaluated by CCK-8 method,live/dead cell double staining method and in vivo anti-tumor experiment in tumor-bearing mice.The anti-infection and pro-healing properties of GOx/BMOFs@PU were evaluated in a mouse model of infected wound.Results The GOx/BMOFs@PU fiber prepared in this study has good biocompatibility.It shows remarkable antibacterial effect and anti-Staphylococcus aureus biofilm ability.In addition,the GOx/BMOFs@PU fiber effectively eliminated tumor cells in vitro and in vivo through synergistic starvation/chemodynamic therapy.It also showed good performance in promoting the healing of infected wounds.Conclusion The GOx/BMOFs@PU composite fiber can inhibit tumor recurrence and promote wound healing and is an excellent candidate material for postoperative treatment of tumor.更多还原