目的 制备负载葫芦素B类沸石咪唑酯骨架材料-8（ZIF-8）纳米粒（cucurbitacin B-loaded ZIF-8 nanoparticles，CuB@ZIF-8 NPs），并对其进行表征和体外抗肝肿瘤药效评价。方法 利用“一锅法”制备CuB@ZIF-8 NPs；利用HPLC法测定葫芦素B载药量及包封率；利用马尔文激光粒度分析、透射电子显微镜（transmission electron microscope，TEM）观察、扫描电子显微镜（scanning electron microscope，SEM）观察、X射线衍射（X-ray diffraction，XRD）分析、傅里叶变换红外光谱（Fourier-transform infrared spectroscopy，FTIR）分析、热重分析（thermogravimetric analysis，TGA）、比表面积法（Brunauer-Emmett-Teller，BET）、动态光散射（dynamic light scattering，DLS）分析和ζ电位分析等对其结构进行表征；离心法考察CuB@ZIF-8 NPs的稳定性和体外释药行为。MTT实验检测纳米粒抑制HepG2细胞增殖能力；荧光显微镜观察纳米粒对HepG2细胞核的形态变化；流式细胞仪检测纳米粒对细胞凋亡率及细胞内活性氧簇（reactive oxygen species，ROS）水平的影响。结果 CuB@ZIF-8 NPs的载药量为（16.62±1.20）%，包封率为（66.73±2.30）%，粒径为（182.43±1.88）nm，ζ电位为（24.80±0.52）mV，具有规则的十二面体结构，比表面积为1 391.10 m²/g；纳米粒的稳定性良好，pH 5.5时体外释放率达77.56%；CuB@ZIF-8处理的HepG2细胞的存活率为（18.82±3.52）%，细胞内ROS含量为（123.61±0.03）%，细胞凋亡率为（98.61±0.02）%。结论 制备的纳米粒形状均一，载药量较高，明显增强药物抗肝肿瘤疗效，为葫芦素B纳米新制剂的开发提供借鉴。

Objective To prepare cucurbitacin B-loaded Zinc-based metal organic skeleton (ZIF-8) nanoparticles (CuB@ZIF-8 NPs), systematically characterize their physicochemical properties, and evaluate their anti-hepatoma activity in vitro. Methods CuB@ZIF-8 NPs were synthesized using a one-pot method. Drug loading capacity and encapsulation efficiency of cucurbitacin B were quantified via HPLC. Physicochemical characterization included Malvern laser particle size analysis, transmission electron microscope (TEM) observation, scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), Brunauer-Emmett-Teller (BET) surface area measurement, dynamic light scattering (DLS), and ζ potential analysis. Stability under physiological conditions and pH-responsive drug release kinetics were evaluated using centrifugation. In vitro anti-hepatoma efficacy was assessed using HepG2 cells: cytotoxicity via MTT assay, apoptosis via Annexin V-FITC/PI staining and nuclear morphological analysis, and intracellular reactive oxygen species (ROS) generation via flow cytometry. Results The optimized CuB@ZIF-8 NPs exhibited a uniform rhombic dodecahedral morphology with a hydrodynamic diameter of (182.43 ±1.88) nm, ζ potential of (24.80 ±0.52) mV, high specific surface area (1 391.10 m²/g), drug loading of (16.62 ±1.20)%, and encapsulation efficiency (EE) of (66.73 ±2.30)%. The nanoparticles demonstrated exceptional colloidal stability and pH-dependent drug release, achieving 77.56% cumulative cucurbitacin B release in acidic buffer (pH 5.5). The survival rate of HepG2 cells treated with CuB@ZIF-8 was (18.82 ±3.52)%, the intracellular ROS content was (123.61 ±0.03)%, and the apoptosis rate was (98.61 ±0.02)%. Conclusion The prepared nanoparticles have uniform shapes and high drug loading capacity, significantly enhancing the therapeutic effect against liver tumors and providing a reference for the development of new cucurbitacin B nano-preparations.

R283.6

国家中医药管理局高水平建设学科项目（zyyzdxk-2023272）