摘要
以2-甲基咪唑(2-MelM)和Zn(NO_(3))_(2)为原料,制备了沸石咪唑骨架-8(ZIF-8)纳米材料,将其作为化疗药物载体,在其内外层分别负载化疗药物环丙沙星(CIP)和紫杉醇(TAX),最后包覆聚多巴胺(PDA)构建了ZIF-8∶CIP@ZIF-8∶TAX@PDA纳米给药平台(ZCZTP)。采用TEM、纳米粒度及Zeta电位分析仪、XRD、EDS对ZCZTP进行了表征,通过CCK-8法评估了ZCZTP的生物安全性和细胞毒性,通过标记罗明丹B(RhB)和激光共聚焦扫描显微镜(CLSM),评价了4T1细胞对ZCZTP的摄取能力。结果表明,ZCZTP粒径均一,且形态规则呈立方体;CIP与TAX分别在载体内外层包覆;ZCZTP的Zeta电位为(–13.23±2.29)mV,其CIP和TAX的载药量分别为4.28%和8.57%,包封率分别为42.8%和85.7%,CIP和TAX的48 h(pH=6.5)药物累积释放量分别为46.0%与61.1%,释放具有pH响应性,在酸性条件下可以释放更多药物;ZCZTP具有良好的生物安全性与血液相容性,质量浓度为400 g/L的ZCZTP对Balb/c小鼠血的溶血率<5%,ZCZTP可以通过内吞作用进入4T1细胞并在溶酶体中积累,经质量浓度为10 mg/L的ZCZTP处理后的4T1细胞存活率较无药物添加的对照组下降62.49%。
Zeolite imidazole-8(ZIF-8)nanomaterial as chemotherapy drug carrier was prepared from 2-methylimidazole(2-MelM)and Zn(NO_(3))_(2),loaded with chemotherapy drugs ciprofloxacin(CIP)and paclitaxel(TAX)in the inner and outer layers,respectively,and finally was coated with polydopamine(PDA)to obtain a ZIF-8∶CIP@ZIF-8∶TAX@PDA nano drug delivery platform(ZCZTP),which was further characterized by TEM,nano particle size and Zeta potential analyzer,XRD and EDS.The biosafety and cytotoxicity of ZCZTP were evaluated by CCK-8 method,and the ZCZTP uptake ability of 4T1 cells was analyzed by labeling with Rhodamine B(RhB)and confocal laser scanning microscopy(CLSM).The results indicated that ZCZTP exhibited a uniform particle size and a regular cubic morphology,with the CIP and TAX loaded on the inner and outer layers,respectively.Moreover,the ZCZTP showed a Zeta potential of(–13.23±2.29)mV,a drug loading capacity for CIP and TAX of 4.28%and 8.57%,respectively,an encapsulation efficiency of 42.8%and 85.7%,respectively,and a cumulative drug release at 48 h(pH=6.5)of 46.0%and 61.1%,respectively.The release was pH responsive and could release more drugs under acidic conditions.ZCZTP also displayed good blood compatibility,with the Balb/c mouse blood hemolysis rate of ZCZTP with a mass concentration of 400 mg/L less than 5%.ZCZTP could enter 4T1 cells through endocytosis and accumulate in lysosomes.The survival rate of 4T1 cells treated by ZCZTP with a mass concentration 10 mg/L decreased by 62.49%compared with control group without addition of medicine.
作者
朱威
徐健祥
蒋京浩
朱利民
ZHU Wei;XU Jianxiang;JIANG Jinghao;ZHU Limin(College of Biological and Medical Engineering,Donghua University,Shanghai 201620,China)
出处
《精细化工》
北大核心
2025年第10期2182-2189,2207,共9页
Fine Chemicals
基金
上海市科学技术委员会项目(22520710400、21WZ2501300、20DZ2254900)
教育部生物医药纺织材料“111项目”(B07024)。
关键词
金属有机框架
沸石咪唑骨架-8
分区载药
化疗
协同治疗
生物工程
metal organic frameworks
zeolite imidazole framework-8
partition drug loading
chemotherapy
synergistic therapy
bioengineering
