高等学校化学学报

高等学校化学学报

• 研究论文 • 上一篇    

橙皮素负载 ZIF-8 的一锅法制备及肿瘤微酸响应释药行为

赵杨1#，朱镇2#，杨柳青3，曹展华1，仲炳文1，庄元1，刘志辉1*
  

  1. 1.吉林大学口腔医院

    2. 镇江市口腔医院 3.福建医科大学附属口腔医院

  • 收稿日期:2026-03-31 修回日期:2026-05-03 网络首发:2026-05-06 发布日期:2026-05-06
  • 通讯作者: 刘志辉 E-mail:liu_zh@jlu.edu.cn
  • 基金资助:
    国自然基金委面上项目（批准号：82370934），镇江市科技计划（批准号：SH2024073）资助

One-Pot Preparation of Hesperetin-Loaded ZIF-8 for Tumor Acidic Microenvironment-Responsive Drug Release

ZHAO Yang1，ZHU Zhen2，YANG Liuqing3，CAO Zhanhuan1，ZHONG Bingwen1，ZHUANG Yuan1，LIU Zhihui1   

  1. 1. Hospital of Stomatology, Jilin University 2. Zhenjiang Stomatological Hospital 3. Affiliated Stomatological Hospital of Fujian Medical University
  • Received:2026-03-31 Revised:2026-05-03 Online First:2026-05-06 Published:2026-05-06
  • Contact: LIU ZHIHUI E-mail:liu_zh@jlu.edu.cn
  • Supported by:
    Supported by the General Program of the National Natural Science Foundation of China (Grant No. 82370934) and the Zhenjiang Municipal Science and Technology Program (Grant No. SH2024073)

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摘要： 采用一锅法将橙皮素（HES）引入 ZIF-8 框架，构建了 HES@ZIF-8 纳米复合材料。采用扫描电子显微镜、透射电子显微镜、X 射线衍射、傅里叶变换红外光谱、氮气吸附-脱附及热重分析等技术，对其形貌、晶体结构、孔结构及热稳定性进行了系统表征，并测定了其载药率及不同 pH 条件下的体外释放行为。结果表明，HES@ZIF-8 成功构建，负载后颗粒仍保持 ZIF-8 规则多面体形貌及特征晶体骨架，说明 HES 的引入未破坏主体框架结构；孔结构参数及热失重行为的变化进一步证实 HES 已有效整合进入 ZIF-8 体系，载药率达 72.0%。体外释药研究显示，HES@ZIF-8 具有显著的 pH 依赖性释放特征，在 pH 7.4、6.5 和 5.5 条件下的累积释放率分别为 42.9%、72.6% 和 92.9%；酸性条件下颗粒骨架明显解离，表明其加速释放与 ZIF-8 的酸诱导结构破坏密切相关。体外细胞实验表明，HES@ZIF-8 在 0–40 μg/mL 的工作浓度范围内对正常成纤维细胞（L929）具有较好的生物相容性；同时，该材料可降低 CAL-27 和 SACC 细胞活力，抑制细胞迁移并促进其凋亡，其中对 SACC 细胞作用更为明显。上述结果表明，HES@ZIF-8 兼具结构保持性负载与肿瘤微酸环境响应释放特征，可为天然小分子/MOF 复合智能递药材料的设计提供实验依据。

关键词: 橙皮素, ZIF-8, 金属有机框架, 纳米复合材料, 酸响应释放

Abstract: Hesperetin (HES) was incorporated into the ZIF-8 framework via a one-pot method to construct HES@ZIF-8 nanocomposites. The morphology, crystal structure, pore structure, and thermal stability were systematically characterized using scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, nitrogen adsorption-desorption, and thermogravimetric analysis . Furthermore, the drug-loading capacity and in vitro release behavior under different pH conditions were evaluated . The results demonstrate the successful construction of HES@ZIF-8, which retained the regular polyhedral morphology and characteristic crystal framework of ZIF-8 after loading, indicating that the introduction of HES did not disrupt the host framework structure. Changes in pore structure parameters and thermal weight loss behavior further confirmed the effective integration of HES into the ZIF-8 system, achieving a drug-loading capacity of 72.0% . In vitro drug release studies revealed that HES@ZIF-8 exhibited a pronounced pH-dependent release profile, with cumulative release rates of 42.9%, 72.6%, and 92.9% at pH 7.4, 6.5, and 5.5, respectively. The significant dissociation of the particle framework under acidic conditions indicates that the accelerated release is closely related to the acid-induced structural disruption of ZIF-8. In vitro cellular experiments showed that HES@ZIF-8 possessed good biocompatibility with normal fibroblasts (L929) within a working concentration range of 0–40 μg/mL. Concurrently, the material decreased the viability of CAL-27 and SACC cells, inhibited cell migration, and promoted apoptosis, with a more pronounced effect observed in SACC cells . These findings indicate that HES@ZIF-8 features both structure-retaining loading and tumor microacidic environment-responsive release, providing an experimental basis for the design of natural small molecule/MOF composite smart drug delivery materials.

Key words: hesperetin, ZIF-8; metal-organic frameworks, nanocomposites, acid-responsive release

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