双重靶向仿生纳米递送系统的构建优化及其体外脑胶质瘤靶向性研究

doi:10.3969/j.issn.1006-7795.2026.03.005

首都医科大学学报 ›› 2026, Vol. 47 ›› Issue (3): 437-448.doi: 10.3969/j.issn.1006-7795.2026.03.005

• 从分子机制到临床应用:创新药物新突破 • 上一篇下一篇

双重靶向仿生纳米递送系统的构建优化及其体外脑胶质瘤靶向性研究

那畅^1,2#,田阳^1,2#,罗舒馨^1,2,张爽^1,3*△,王瑶琪^1,2*△

1.首都医科大学药学院药剂学系，北京 100069；2.首都医科大学基础-临床联合实验室（儿童肿瘤发病机制与创新药物研究实验室），北京 100069；3.首都医科大学临床-基础合作平台（牙周黏膜免疫分子机制及精准调控策略研究联合实验室），北京 100069

收稿日期:2026-02-02 修回日期:2026-03-27 出版日期:2026-06-21 发布日期:2026-06-26
通讯作者: 张爽, 王瑶琪 E-mail:zshuang@ccmu.edu.cn；wangyaoqi@ccmu.edu.cn
基金资助:
国家自然科学基金项目（82304390），首都医科大学科创中心协同创新项目（CX25YZ02, CX25XT04）。

Optimization of a dual-targeting biomimetic nano-delivery system and in vitro evaluation of its targeting efficacy in glioblastoma

Na Chang^1,2#,Tian Yang^1,2#, Luo Shuxin^1,2, Zhang Shuang1^,3*△, Wang Yaoqi^1,2*△

1.Department of Pharmaceutics，School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, China；2.Laboratory for Clinical Medicine (Laboratory of Pediatric Tumor Pathogenesis and Innovative Drug Research), Capital Medical University, Beijing 100069, China；3. Collaboration Platform for Clinical Medicine (Joint Laboratory for Molecular Mechanisms of Periodontal Mucosal Immunity and Precision Modulation Strategies), Capital Medical University, Beijing 10069, China

Received:2026-02-02 Revised:2026-03-27 Online:2026-06-21 Published:2026-06-26
Supported by:
This study was supported by National Natural Science Foundation of China (82304390)， Grants from the Chinese Institutes for Medical Research, Beijing (CX25YZ02，CX25XT04).

摘要/Abstract

摘要： 目的构建基于表没食子儿茶素没食子酸酯（epigallocatechin gallate,EGCG）-锌离子（Zn）超分子纳米载体（EZ NPs），包被angiopep-2（ANG-2）修饰脂质体与胶质瘤细胞膜融合膜的双重靶向纳米系统（dual-targeting nano-delivery system,ANG-2-CMLNPs），以实现靶向Survivin的小干扰RNA（small interfering Survivin,si-Survivin）的高效负载与脑内递送，并评价其理化特性及体外脑胶质瘤靶向性和抗肿瘤活性。方法采用动态光散射、透射电镜、琼脂糖凝胶电泳、荧光分光光度计及流式细胞术，系统表征纳米系统的粒径、电位、形貌、包封率、稳定性，细胞靶向摄取行为及抗肿瘤活性。利用U87 MG胶质瘤细胞及HCMEC/D3内皮细胞模型，评价其跨血脑屏障(blood-brain barrier,BBB)能力、肿瘤细胞靶向效率及体外抗增殖活性。结果成功制备粒径约（89.33±13.25）nm、电位（-11.17±0.70） mV的ANG-2-CMLNPs。EZ NPs与siRNA质量比为125∶1时，包封率达（98.98±1.01）%。透射电镜显示其呈球形且具完整膜结构。流式结果表明，ANG-2-CMLNPs在HCMEC/D3细胞中摄取显著，具跨BBB潜力；其在U87 MG细胞摄取效率较对照组显著提升（P<0.001）。脂质体与细胞膜质量比为1∶5时，系统在两种细胞中摄取达最佳平衡。MTT结果显示，ANG-2-CMLNPs可浓度依赖性抑制U87 MG增殖，100 nmol/L时，细胞存活率降至28.4%。结论本研究成功构建兼具跨BBB与肿瘤靶向能力的纳米递药系统，其稳定性好、包封率高、靶向性显著。优化的膜融合比例（1∶5）为双重靶向功能的协同实现提供了关键参数，为胶质瘤RNA干扰治疗提供了新策略。

关键词: 神经胶质瘤, 血管生成素-2, 脂质融合膜, 小干扰RNA, EGCG金属纳米粒, 仿生纳米系统

Abstract: Objective To construct a dual-targeting nano-delivery system (ANG-2-CMLNPs) based on an epigallocatechin gallate (EGCG)-Zn supramolecular nanocarrier coated with a fusion membrane comprising angiopep-2-modified liposomes and glioma cell membranes for efficient loading and brain delivery of si-Survivin. Methods Dynamic light scattering, transmission electron microscopy(TEM), agarose gel electrophoresis, fluorescence spectrophotometry, and flow cytometry were used to systematically characterize the particle size, Zeta potential, morphology, encapsulation efficiency, stability, and cellular targeting, uptake behavior of the nano-system. Models of U87 MG glioma cells and HCMEC/D3 endothelial cells were used to evaluate the system's blood-brain barrier（BBB） penetration capability, tumor cell targeting efficiency, and in vitro anti-proliferative activity. Results ANG-2-CMLNPs with an average particle size of approximately (89.33±13.25) nm and a Zeta potential of(-11.17±0.70) mV were prepared. The optimal encapsulation efficiency［(98.98±1.01)%］ was attained at an EZ NP/siRNA mass ratio of 125∶1. TEM confirmed a spherical shape with an intact membrane structure. Flow cytometry results indicated significant uptake of ANG-2-CMLNPs by HCMEC/D3 cells, demonstrating potential for BBB penetration; its uptake efficiency in U87 MG cells was significantly higher than in the control groups (P<0.001). When the mass ratio of liposomes to cell membrane was 1∶5, the system achieved optimal uptake balance. MTT results showed that ANG-2-CMLNPs inhibited U87 MG cell proliferation in a concentration-dependent manner, with cell viability decreasing to 28.4% at an siRNA concentration of 100 nmol/L. Conclusion This study constructed a nano-drug delivery system with BBB-crossing and tumor-targeting capabilities, exhibiting good stability, high encapsulation efficiency, and significant targeting ability. The optimized membrane fusion ratio (1∶5) provided a key parameter for the synergistic realization of dual-targeting functions, offering a new strategy for RNAi therapy of glioma.

Key words: glioblastoma, angiopoietin-2, lipid fusion membrane, small interfering RNA, EGCG metal nanoparticles, biomimetic nanosystem

中图分类号:

R943
R739.41

那畅, 田阳, 罗舒馨, 张爽, 王瑶琪. 双重靶向仿生纳米递送系统的构建优化及其体外脑胶质瘤靶向性研究[J]. 首都医科大学学报, 2026, 47(3): 437-448.

Na Chang, Tian Yang, Luo Shuxin, Zhang Shuang, Wang Yaoqi. Optimization of a dual-targeting biomimetic nano-delivery system and in vitro evaluation of its targeting efficacy in glioblastoma[J]. Journal of Capital Medical University, 2026, 47(3): 437-448.

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双重靶向仿生纳米递送系统的构建优化及其体外脑胶质瘤靶向性研究

Optimization of a dual-targeting biomimetic nano-delivery system and in vitro evaluation of its targeting efficacy in glioblastoma

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