摘要
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(BrunauerEmmett-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)m V,具有规则的十二面体结构,比表面积为1 391.10 m^(2)/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@ZIF8 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),andζpotential 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 VFITC/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,ζpotential of(24.80±0.52)mV,high specific surface area(1391.10 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.
作者
徐晓涵
张慧中
阮意丹
李诗曼
张可
王雯琪
杨静雯
李文静
王欣竹
董晓旭
倪健
XU Xiaohan;ZHANG Huizhong;RUAN Yidan;LI Shiman;ZHANG Ke;WANG Wenqi;YANG Jingwen;LI Wenjing;WANG Xinzhu;DONG Xiaoxu;NI Jian(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China)
出处
《中草药》
北大核心
2025年第16期5739-5748,共10页
Chinese Traditional and Herbal Drugs
基金
国家中医药管理局高水平建设学科项目(zyyzdxk-2023272)。
关键词
葫芦素B
锌基金属有机骨架ZIF-8
纳米粒
抗肝肿瘤
稳定性
体外释药行为
细胞增殖能力
细胞凋亡
活性氧簇
cucurbitacin B
Zinc-based metal organic skeleton ZIF-8
nanoparticles
anti-liver tumor
stability
drug release behavior in vitro
cell proliferation ability
apoptosis
reactive oxygen species
