结肠癌细胞膜仿生铜基金属有机框架对DC的激活和促血管新生作用  

Activation of DC and promotion of neovascularization by colon cancer membrane biomimetic copper-based metal-organic framework

作　　者：张欣怡 张梦亚 张停琳 高洁 ZHANG Xinyi;ZHANG Mengya;ZHANG Tinglin;GAO Jie(Institute of Translation Medicine,Shanghai University,Shanghai 200444,China;Clinical Research Unit,the First Affiliated Hospital of Naval Medical University,Shanghai 200433,China;Key Laboratory of Marine Medicine and Drug Transformation,the First Affiliated Hospital of Naval Medical University,Shanghai 200433,China)

机构地区：[1]上海大学转化医学研究院,上海200444 [2]海军军医大学第一附属医院临床研究中心,上海200433 [3]海军军医大学第一附属医院上海市航海医学与药械转化重点实验室,上海200433

出　　处：《中国肿瘤生物治疗杂志》2024年第6期552-557,共6页Chinese Journal of Cancer Biotherapy

基　　金：国家自然科学基金(No.82072051)。

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。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 copper-based 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(P<0.01).In addition,both MOF and MOF@CCM could promote the formation of tubular structures in HUVEC cells(P<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.

关 键 词：结直肠癌 细胞膜 金属有机框架 肿瘤疫苗 肿瘤免疫 

分 类 号：R735.35[医药卫生—肿瘤] R73-36[医药卫生—临床医学]