[关键词]
[摘要]
目的:探讨结肠癌细胞膜包裹的铜基金属有机框架(MOF@CCM)的DC激活和促进血管新生的潜力。方法:首先构建 1,3,5-苯三甲酸铜(Ⅱ)铜基金属有机框架(HKUST-1),在其外层包覆结肠癌CT26细胞膜,获得MOF@CCM,对其进行物理表征。 用CCK-8法研究MOF@CCM的生物相容性,流式细胞术分析MOF@CCM对DC2.4成熟比例的影响,以验证MOF@CCM激活免疫 细胞的潜力。通过血管生成实验验证MOF@CCM促人脐静脉内皮细胞(HUVEC)形成血管的能力。结果:成功制备了MOF@CCM, 透射电镜观察显示其形状近似圆形,具有明显的核壳结构。MOF@CCM的平均粒径为(150.5±7.89) nm,平均Zeta 电位为–(5.12± 1.67) mV。体外实验结果显示,与对照组相比,MOF@CCM能够显著提高DC2.4成熟的比例(P<0.01)。此外,MOF和MOF@CCM 均能促进HUVEC形成管状结构(P<0.05或P<0.01),且细胞膜修饰对MOF的促血管新生作用没有影响。结论:制备的MOF@CCM 在所使用的剂量下具有良好的细胞相容性,能够显著促进DC2.4的成熟和促进HUVEC血管生成,有望成为抗结肠癌和促进组织修 复的双功能治疗平台。
[Key word]
[Abstract]
Objective: To explore the potential of colon cancer cell membrane-coated copper-based metal-organic frameworks (MOF@CCM) in anti-tumor activities and promotion of tissue healing. Methods: Copper (Ⅱ) 1, 3, 5-benzenetricarboxylate copperbased metal-organic framework (HKUST-1) was constructed, and coated with colon cancer cell CT26 membrane on its outer layer to obtain MOF@CCM, which was physically characterized. The biocompatibility of MOF@CCM was determined by CCK-8 assay, and the effect of MOF@CCM on the proportion of DC2.4 maturation was analyzed by flow cytometry to verify the potential of MOF@CCM in activating immune cells. Angiogenesis experiments was used to verify the potential of MOF@CCM in promoting HUVEC to form blood vessels. Results: MOF@CCM was successfully synthesized. Transmission electron microscopy showed that its shape was approximately circular and had an obvious core-shell structure. The average particle size of MOF@CCM was (150.5±7.89) nm, and the average Zeta potential was -(5.12±1.67) mV. The results of in vitro experiments showed that compared with the control group, MOF@CCM could significantly increase the proportion of DC2.4 maturation ( PP<0.05 or P<0.01), and cell membrane modification had no significant effect on the pro-neovascularization effect of MOF. Conclusion: The synthesized MOF@CCM has good cell compatibility at the dose used and can significantly promote the maturation of DC2.4 cells and HUVEC angiogenesis. It is expected to become a bifunctional treatment platform for anti-colon cancer treatment and tissue repair promotion.
[中图分类号]
[基金项目]
国家自然科学基金(No. 82072051)