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重楼皂苷VI金属有机骨架纳米制剂的制备及抗肿瘤活性初步评价

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中草药 | 药剂与工艺 2026,57(9): 3313-3328

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中草药 |药剂与工艺 2026 , 57 (9) : 3313 -3328

重楼皂苷VI金属有机骨架纳米制剂的制备及抗肿瘤活性初步评价

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陈红月¹, 尹东阁¹, 林舒婷¹, 荆霄鸿¹, 孙宇菲¹, 常榕蓉¹, 冯洋¹, 吴辰瑶¹, 曲昌海¹, 董晓旭¹, 倪健¹, 尹兴斌¹

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通讯作者:

倪健

作者简介:

陈红月: 陈红月,女,硕士研究生,主要从事中药新剂型与新技术的研究。E-mail:20240935229@bucm.edu.cn

Preparation and preliminary evaluation of anti-tumor activity of polyphyllin VI metal-organic framework nanoparticles

CHEN Hongyue, YIN Dongge, LIN Shuting, JING Xiaohong, SUN Yufei, CHANG Rongrong, FENG Yang, WU Chenyao, QU Changhai, DONG Xiaoxu, NI Jian, YIN Xingbin

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doi: 10.7501/j.issn.0253-2670.2026.09.006

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摘要

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目的采用等网状金属有机骨架-1（isoreticular metal-organic framework-1，IRMOF-1）包载中药抗肿瘤活性成分重楼皂苷VI（polyphyllin VI，PPVI）并包覆穿膜肽构建靶向纳米制剂（PEG-PTP/PPVI@IRMOF-1），对其进行表征和体外抗肿瘤药效初步评价。方法通过“三乙胺沉淀法”和“反应包覆法”制备PEG-PTP/PPVI@IRMOF-1；利用粒径与ζ电位测定、扫描电子显微镜（scanning electron microscopy，SEM）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）、气体吸附（Brunauer-Emmett-Teller，BET）分析、X射线光电子能谱（X-ray photoelectron spectroscopy，XPS）分析对其粒径、形貌、热稳定性、比表面积等性质进行表征；溶血实验评价纳米材料的生物安全性；CCK-8法评价材料安全性并检测纳米粒对人胰腺癌PANC-1细胞增殖的影响；荧光显微镜观察材料及纳米粒对PANC-1细胞核形态的影响；激光共聚焦实验考察纳米粒的体外靶向性；克隆形成实验、划痕实验考察纳米粒对细胞增殖、迁移的影响；流式细胞仪检测纳米粒对细胞凋亡率和细胞内活性氧（reactive oxygen species，ROS）水平的影响；激光共聚焦实验考察纳米粒对细胞线粒体膜电位（mitochondrial membrane potential，MMP）的影响。结果成功制备了靶向纳米粒PEG-PTP/PPVI@IRMOF-1，为干燥的白色粉末状。纳米粒外观为类球形，粒径为（177.47±3.97）nm，ζ电位为（−7.94±0.14）mV；PPVI@IRMOF-1的载药量为（43.02±0.08）%；纳米材料具有良好的生物安全性；靶向肽修饰后能够明显增强肿瘤细胞对药物的摄取，显著抑制细胞增殖，促进细胞中ROS的产生和MMP的下降，诱导肿瘤细胞的凋亡。结论制备的纳米粒形状均一，载药量较高，安全性良好，增强了PPVI的抗肿瘤疗效，能够为PPVI抗肿瘤制剂的开发提供参考。

关键词

重楼皂苷VI / 金属有机骨架材料 / 靶向制剂 / 抗肿瘤 / 胰腺癌

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Objective A targeted nanoformulation (PEG-PTP/PPVI@IRMOF-1) was constructed by encapsulating the traditional Chinese medicine antitumor active component polyphyllin VI (PPVI) within isoreticular metal-organic framework-1 (IRMOF-1) and coating it with a cell-penetrating peptide. The study aims to characterize the nanoformulation and conduct a preliminary evaluation of its in vitro antitumor efficacy. Methods PEG-PTP/PPVI@IRMOF-1 was fabricated via the “triethylamine precipitation method” and “reaction coating method”; The physicochemical properties of the nanoformulation, including particle size, morphology, thermal stability, and specific surface area, were characterized by particle size and ζ-potential measurement, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), Brunauer-Emmett-Teller (BET) gas adsorption, and X-ray photoelectron spectroscopy (XPS). Hemolysis assay was used to assess the biosafety of nanomaterials. CCK-8 assay was adopted to evaluate the material safety and detect the effect of nanoparticles on the proliferation of human pancreatic cancer PANC-1 cells. The effect of materials and nanoparticles on the nuclear morphology of PANC-1 cells was observed by fluorescence microscopy; The targeting capability of the nanoparticles ex vivo was assessed by laser scanning confocal microscopy; The effects of nanoparticles on cell proliferation and migration were examined using colony formation and scratch assays, respectively; Flow cytometry was employed to determine the impact of the nanoparticles on the cellular apoptosis rate and intracellular reactive oxygen species (ROS) levels; The effect of nanoparticles on the mitochondrial membrane potential (MMP) of cells was examined by laser confocal microscopy. Results The targeted nanoformulation PEG-PTP/PPVI@IRMOF-1 was successfully fabricated as a dry white powder. The nanoparticles exhibited a quasi-spherical morphology with an average particle size of about (177.47 ± 3.97) nm and a ζ potential of (−7.94 ± 0.14) mV; The drug loading capacity (DLC) of PPVI@IRMOF-1 was (43.02 ± 0.08)%; The nanomaterial showed excellent biocompatibility; Notably, targeted peptide modification can significantly enhance the drug uptake of tumor cells, significantly inhibit cell proliferation, promote the production of ROS and the decrease of MMP in cells, and induce apoptosis of tumor cells. Conclusion The prepared PEG-PTP/PPVI@IRMOF-1 nanoparticles possess uniform morphology, high drug loading capacity, and good biocompatibility. Moreover, the nanoformulation significantly enhances the in vitro antitumor efficacy of PPVI, providing a reference for the development of PPVI-based antitumor formulations.

Key words

polyphyllin VI / metal-organic framework materials / targeted nanoformulation / anti-tumor / pancreatic cancer

引用本文

陈红月, 尹东阁, 林舒婷, 荆霄鸿, 孙宇菲, 常榕蓉, 冯洋, 吴辰瑶, 曲昌海, 董晓旭, 倪健, 尹兴斌. 重楼皂苷VI金属有机骨架纳米制剂的制备及抗肿瘤活性初步评价. 中草药, 2026 , 57 (9) : 3313 -3328 . DOI: 10.7501/j.issn.0253-2670.2026.09.006

CHEN Hongyue, YIN Dongge, LIN Shuting, JING Xiaohong, SUN Yufei, CHANG Rongrong, FENG Yang, WU Chenyao, QU Changhai, DONG Xiaoxu, NI Jian, YIN Xingbin. Preparation and preliminary evaluation of anti-tumor activity of polyphyllin VI metal-organic framework nanoparticles[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (9) : 3313 -3328 . DOI: 10.7501/j.issn.0253-2670.2026.09.006

基金

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福建省自然科学基金项目(2025J01958)

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宋深磊.带您了解“癌中之王”:胰腺癌[J].抗癌之窗,2025(2):40-43.
Park W, Chawla A, O’Reilly E M. Pancreatic cancer:A review[J]. Jama, 2021, 326(9):851.
Tempero M A, Malafa M P, Chiorean E G, et al. Pancreatic adenocarcinoma, version 1.2019[J]. J Natl Compr Canc Netw, 2019, 17(3):202-210.
闫靖楠,宋忠阳,祁亚锋,等.中药调控肿瘤免疫微环境的作用及机制研究进展[J].中草药, 2025, 56(17):6477-6492.
Lin Z F, Liu Y T, Li F Y, et al. Anti-lung cancer effects of polyphyllin VI and VII potentially correlate with apoptosis in vitro and in vivo:Anti-lung cancer effects of polyphyllin VI and VII[J]. Phytother Res, 2015, 29(10):1568-1576.
李茂蓉,张辉.重楼皂苷VI通过调控SNRPD1抑制肝癌细胞增殖的机制研究[J].上海中医药杂志, 2024,58(4):79-85.
Wang P W, Yang Q B, Du X Y, et al. Targeted regulation of Rell2 by microRNA-18a is implicated in the antimetastatic effect of polyphyllin VI in breast cancer cells[J]. Eur J Pharmacol, 2019, 851:161-173.
王晓菲,李鹏,杨玥,等.重楼皂苷抗炎、抗氧化及抗肿瘤作用机制研究进展[J].药物评价研究, 2023,46(12):2699-2708.
Dhakshinamoorthy A, Asiri A M, García H. Metal-organic framework(MOF)compounds:Photocatalysts for redox reactions and solar fuel production[J]. Angew Chem Int Ed, 2016, 55(18):5414-5445.
Furukawa H, Cordova K E, O’Keeffe M, et al. The chemistry and applications of metal-organic frameworks[J]. Science, 2013, 341(6149):1230444.
Meek S T, Greathouse J A, Allendorf M D. Metal-organic frameworks:A rapidly growing class of versatile nanoporous materials[J]. Adv Mater, 2011, 23(2):249-267.
Wang K X, Cai M R, Yin D G, et al. Functional metalorganic framework nanoparticles loaded with polyphyllin I for targeted tumor therapy[J]. J Sci Adv Mater Devices,2023, 8(2):100548.
蔡梦如,姚宇,尹东阁,等.金属有机骨架材料在中药研究的应用进展[J].中草药, 2021, 52(16):5028-5038.
Chen G S, Luo J Y, Cai M R, et al. Investigation of metalorganic framework-5(MOF-5)as an antitumor drug oridonin sustained release carrier[J]. Molecules, 2019,24(18):3369.
Cai M R, Liang W L, Wang K X, et al. Aperture modulation of isoreticular metal organic frameworks for targeted antitumor drug delivery[J]. ACS Appl Mater Interfaces, 2022, 14(32):36366-36378.
Cai M R, Qin L Y, You L T, et al. Functionalization of MOF-5 with mono-substituents:Effects on drug delivery behavior[J]. RSC Adv, 2020, 10(60):36862-36872.
Li Y, Wang H B, Wang K, et al. Targeted co-delivery of PTX and TR3 siRNA by PTP peptide modified dendrimer for the treatment of pancreatic cancer[J]. Small, 2017,13(2):1602697.
Gao Y, Xie J J, Chen H J, et al. Nanotechnology-based intelligent drug design for cancer metastasis treatment[J].Biotechnol Adv, 2014, 32(4):761-777.
Li Y Q, Zheng Y T, Lai X Y, et al. Biocompatible surface modification of nano-scale zeolitic imidazolate frameworks for enhanced drug delivery[J]. RSC Adv,2018, 8(42):23623-23628.
Ray Chowdhuri A, Bhattacharya D, Sahu S K. Magnetic nanoscale metal organic frameworks for potential targeted anticancer drug delivery, imaging and as an MRI contrast agent[J]. Dalton Trans, 2016, 45(7):2963-2973.
Zhang Y, Wang L, Liu L, et al. Engineering metal-organic frameworks for photoacoustic imaging-guided chemo-/photothermal combinational tumor therapy[J]. ACS Appl Mater Interfaces, 2018, 10(48):41035-41045.
桑楠.了解胰腺癌的病因与风险[J].人人健康,2025(20):78-79.
陈红月,尹东阁,林舒婷,等.重楼皂苷Ⅵ的现代研究进展[J/OL].中国实验方剂学杂志,(2025-10-22)[2026-04-13]. https://doi.org/10.13422/j.cnki.syfjx.20252125.
Zhang Y, Bao Y L, Wu Y, et al. Alantolactone induces apoptosis in RKO cells through the generation of reactive oxygen species and the mitochondrial pathway[J]. Mol Med Rep, 2013, 8(4):967-972.
何旻倩,张诗妍,沈逸竹,等.细胞凋亡机制及其信号通路研究进展[J].生物化工, 2025, 11(4):228-231.

2026年第57卷第9期

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doi: 10.7501/j.issn.0253-2670.2026.09.006

接收时间：2025-12-05
首发时间：2026-09-09

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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