目的 制备柴胡皂苷D（saikosaponins D，SSD）与大麻二酚（cannabidiol，CBD）自组装纳米粒（SSD-CBD），并初步探究其体外抗肝癌机制。方法 采用纳米共沉淀法，以3∶1（投料质量比）制备SSD-CBD自组装纳米粒，利用X射线光电子能谱（X-ray photoelectron spectroscopy，XPS）、傅里叶变换红外光谱（Fourier transform infrared spectroscopy，FTIR）及二维核磁共振氢谱（¹H-¹H nuclear overhauser enhancement spectroscopy，¹H-¹H NOESY）等多技术表征其组装机制；通过透射电子显微镜（transmission electron microscope，TEM）、动态光散射（dynamic light scattering，DLS）等技术评价其理化性质；采用MTT法、流式细胞术（Annexin V-FITC/PI染色）、天冬氨酸特异性的半胱氨酸蛋白水解酶（cysteinyl aspartate specific proteinase，Caspase）活性测定等手段系统评价其体外抗肿瘤活性、凋亡诱导效应及初步机制。结果 该组装体通过氢键和疏水作用自组装形成，SSD与CBD表现出协同效应（CI＝0.79）；SSD-CBD纳米粒还具有pH值响应释药特性，在肿瘤微环境（pH 6.8）中特异性释药，而在正常生理环境（pH 7.4）保持稳定；机制研究表明，其主要通过激活线粒体凋亡途径诱导HepG2细胞死亡。结论 构建的SSD-CBD自组装纳米粒，提供了一种可同步改善CBD递送效率、实现精准协同给药的无载体策略，为基于SSD的智能纳米药物开发提供了实验依据。

Objective To prepare a self-assembled nanoparticles of saikosaponin D (SSD) and cannabidiol (CBD) and preliminarily investigate their anti-hepatoma mechanism in vitro. Methods The SSD-CBD self-assembled nanoparticles were constructed using the nano co-precipitation method at a mass ratio of 3∶1, and their assembly mechanisms were characterized by techniques including X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and ¹H-¹H nuclear overhauser enhancement spectroscopy (¹H-¹H NOESY). Its physicochemical properties were evaluated by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The antitumor activity, apoptosis induction, and preliminary mechanisms were systematically assessed by MTT assay, flow cytometry (Annexin V-FITC/PI staining), and cysteinyl aspartate specific proteinase (Caspase) activity assays. Results The assembly was self-assembled through hydrogen bonding and hydrophobic interactions, with SSD and CBD showing a synergistic effect against HepG2 cells (CI = 0.79). It exhibited pH-responsive drug release, specifically releasing drugs in the tumor microenvironment (pH 6.8) while remaining stable at normal physiological environment (pH 7.4). Mechanistic studies indicated that it primarily induced HepG2 cell death by activating the mitochondrial apoptotic pathway. Conclusion The constructed SSD-CBD self-assembled nanoparticles offer a carrier-free strategy that can simultaneously improve the delivery efficiency of CBD and achieve precise collaborative drug delivery, providing an experimental basis for the development of intelligent nanomedicine based on SSD.

R283.6

西藏自治区重点研发计划（XZ202401ZY0020）；药用植物种质资源库建设（2021-I2M-1-032）；国家岗位产业体系专家项目（CARS-21）；四川省区域创新合作项目（2026YFHZ0163）