目的 不同类型金属有机骨架材料（metal organic frameworks，MOFs）制备工艺优化及筛选，用于负载抗肿瘤单体成分雷公藤红素（celastrol，Cel），从而改善其生物利用度并增强抗肿瘤药效。方法 以粒径大小为指标，单因素考察结合正交试验优化MOFs制备工艺，选择最佳MOFs；吸附法负载雷公藤红素，单因素优化载药工艺，CCK-8法初步评价其抗肿瘤细胞药效。结果 UIO-66最佳工艺为苯甲酸为调节剂，投料比1∶1，溶剂60 mL，溶剂热法反应24 h，粒径（172.3±3.0）nm，多分散指数（polydispersity index，PDI）为0.166±0.023；ZIF-8最佳工艺为投料比1∶50，水10 mL，室温密闭搅拌30 min，粒径（154.0±1.4）nm，PDI为0.245±0.060；MIL-101（Fe）最佳工艺为投料比1∶1，溶剂10 mL，溶剂热法反应24 h，粒径（553.5±36.2）nm，PDI为0.642±0.109；选择ZIF-8进行雷公藤红素的包载，最佳载药工艺为ZIF-8与雷公藤红素比例2∶1，载药时间24 h，药物质量浓度为1 mg/mL，制得ZIF-8@Cel粒径为（164.9±8.0）nm，PDI为0.297±0.029，载药量为（23.47±0.26）%；实验剂量下ZIF-8对HepG2细胞无毒，雷公藤红素处理HepG2细胞24 h的半数致死浓度（half-inhibitory concentration，IC₅₀）为3.821 μg/mL，ZIF-8@Cel的IC₅₀值为3.289 μg/mL（以雷公藤红素含量计）。结论 优选的ZIF-8材料制备及载药工艺稳定可行，粒子形状规则，晶型良好，分布均匀，载药量高，生物安全性好，载药后可明显增强药物药效，为雷公藤红素抗肿瘤纳米制剂的研究提供了基础。

Objective The preparation process optimization and screening of different types of metal organic frameworks (MOFs), which are used to load the antitumor monomer celastrol (Cel), so as to improve its bioavailability and enhance the antitumor efficacy. Methods Taking the particle size as the index, the preparation process of MOFs was optimized by single factor investigation and orthogonal test, and then the best MOFs was selected. Celastrol was loaded by adsorption method, and the drug loading process was optimized by single factor experiment. The anti-tumor effect was preliminarily evaluated by CCK-8 method. ResultsThe optimum process of UIO-66 is as follows:benzoic acid as regulator, feed ratio 1:1, solvent 60 mL, solvothermal reaction for 24 h, particle size (172.3 ±3.0) nm, PDI 0.166 ±0.023. The optimum process of ZIF-8 is as follows:feed ratio 1:50, water 10 mL, airtight stirring at room temperature for 30 min, particle size (154.0 ±1.4) nm and PDI 0.245 ±0.060. The optimum process of MIL-101(Fe) is as follows:the feed ratio is 1:1, the solvent is 10 mL, the solvothermal reaction is 24 h, the particle size is (553.5 ±36.2) nm, and the PDI is 0.642 ±0.109. ZIF-8 was selected for the encapsulation of celastrol. The optimal drug loading process was that the ratio of ZIF-8 to celastrol was 2:1, the drug loading time was 24 h, and the drug concentration was 1 mg/mL. The particle size of ZIF-8@Cel was (164.9 ±8.0) nm, the PDI was 0.297 ±0.029, and the drug loading was (23.47 ±0.26)%. ZIF-8 was non-toxic to HepG2 cells at the experimental dose. The IC₅₀ value of HepG2 cells treated with celastrol for 24 h was 3.821 μg/mL, and the IC₅₀ value of ZIF-8@Cel was 3.289 μg/mL (calculated by celastrol content). Conclusion The optimized ZIF-8 material has stable and feasible preparation and drug loading process, regular particle shape, good crystal form, uniform distribution, high drug loading and good biosafety. ZIF-8@Cel can significantly enhance the drug cell efficacy, which provides a basis for the research of celastrol antitumor nano preparation.

R283.6

中央级公益性科研院所基本科研业务费专项资金资助（ZXKT21012）；中央级公益性科研院所基本科研业务费专项资金资助（ZZ13- 035-08）；中央级公益性科研院所基本科研业务费专项资金资助（CI2021A04301）；中央级公益性科研院所基本科研业务费专项资金资助（ZZ13-YQ-059）