负载环丙沙星和紫杉醇的ZIF-8纳米给药平台的构建与性能

Construction and Performance of ZIF-8 Nanodrug Delivery Platform loaded with Ciprofloxacin and Paclitaxel

摘要:

以2-甲基咪唑（2-MelM）和硝酸锌为原料，制备沸石咪唑骨架-8（ZIF-8）纳米材料作为化疗药物载体，将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）构建纳米给药平台ZIF-8∶CIP@ZIF-8∶TAX@PDA（ZCZTP）的纳米颗粒。采用TEM、纳米粒度电位仪、XRD等对ZCZTP进行表征，通过CCK-8法评估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4T1细胞对ZCZTP的摄取能力。结果表明，ZCZTP粒径均一（单层95 nm左右），且形态规则呈立方体样；EDS表明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）的累积药物释放量分别为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，400 μg/mL的ZCZTP对Balb/c小鼠血的溶血率低于5%，ZCZTP可以通过内吞作用进入4T1细胞并在溶酶体中积累，经10 ug/mL的ZCZTP处理后的4T1细胞存活率下降62.49%。

Abstract:

Using 2-methylimidazole (2-MelM) and zinc nitrate as raw materials, zeolite imidazole-8 (ZIF-8) nanomaterials were prepared as chemotherapy drug carriers. The inner and outer layers were loaded with chemotherapy drugs ciprofloxacin (CIP) and paclitaxel (TAX), respectively. Finally, polydopamine (PDA) was coated to construct a nano drug delivery platform ZIF-8: CIP@ZIF-8 ∶ TAX@PDA (ZCZTP) nanoparticles. Characterization of ZCZTP was carried out using TEM, nano particle potential analyzer, XRD, etc. The biosafety and cytotoxicity of ZCZTP were evaluated by CCK-8 method. The uptake ability of 4T1 cells towards ZCZTP was evaluated by labeling with Rhodamine B (RhB) and confocal laser scanning microscopy (CLSM). The results indicate that ZCZTP has a uniform particle size (around 95 nm for a single layer) and a regular cubic morphology; EDS indicates that CIP and TAX are coated on the inner and outer layers of the carrier, respectively; The Zeta potential of ZCZTP is -13.23 ± 2.29 mV, and its drug loading capacity for CIP and TAX is 4.28% and 8.57%, respectively. The encapsulation efficiency is 42.8% and 85.7%, respectively. The cumulative drug release of CIP and TAX at 48 hours (pH=6.5) is 46.0% and 61.1%, respectively. The release is pH responsive and can release more drugs under acidic conditions; ZCZTP has good biocompatibility and blood compatibility. The hemolysis rate of 400 μ g/mL ZCZTP on Balb/c mouse blood is less than 5%. ZCZTP can enter 4T1 cells through endocytosis and accumulate in lysosomes. After treatment with 10 ug/mL ZCZTP, the survival rate of 4T1 cells decreased by 62.49%.