| 莫春红,杨建英,陈燕宏,李鳗亭,郭桐彤,李新春.双重响应二硫化钼纳米载药体系的制备及其性能研究[J].现代生物医学进展英文版,2020,(23):4407-4412. |
| 双重响应二硫化钼纳米载药体系的制备及其性能研究 |
| Preparation and Properties of Dual Response MoS2 Nanodrug Loading System |
| Received:May 30, 2020 Revised:June 25, 2020 |
| DOI：10.13241/j.cnki.pmb.2020.23.002 |
| 中文关键词: 纳米载药系统 阿霉素 双重响应性 药物释放 |
| 英文关键词: Nanodrug loading system Doxorubicin Dual responsiveness Drug release |
| 基金项目:国家自然科学基金项目（21665004）；广西自然科学基金项目（2018GXNSFAA138022）；广西高等教育本科教学改革工程项目（2019JGA138） |
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| 中文摘要: |
| 摘要 目的：制备肿瘤微环境响应释放的靶向二硫化钼纳米载药体系，并评价其载药量和释药性能。方法：以水热法合成的MoS2纳米片为基底，利用MoS2纳米片上的S空缺位点连接硫辛酸聚乙二醇羧酸，然后通过酰胺反应连接精氨酸-甘氨酸-天冬氨酸（RGD）靶向分子，再连接上交联剂3-(2-吡啶二硫代)丙酸N-琥珀酰亚胺酯（SPDP），得到药物载体MoS2-PEG-RGD-SPDP（MPRS），MPRS进一步与巯基化的阿霉素（DOX）反应，形成MPRS-DOX纳米载药体系。通过透射电子显微镜（TEM），X-射线光电子能谱仪（XPS）以及纳米粒度电位仪对合成的材料进行表征；利用紫外可见分光光度计测试MPRS的载药性能，采用荧光分光光度计考察MPRS-DOX的释药性能。结果：成功合成MPRS-DOX纳米载药体系，其粒径大小在200 nm左右，Zeta电位为+28.2 mV；其载药效率为86.8%，载药量为53.5%。体外释药实验表明，在10 mM 谷胱甘肽（GSH）和pH=5.5的条件下DOX释放量最多。结论：成功制备了粒径合适的MPRS-DOX纳米载药体系，MPRS-DOX具有GSH和pH双重响应性，可实现预期的模拟肿瘤微环境内控制释放药物。这种GSH和pH双重响应的纳米载药体系为新一代刺激响应型纳米载药系统的构建提供了新的思路。 |
| 英文摘要: |
| ABSTRACT Objective: A targeted MoS2 nanodrug loading system that responds to the tumor microenvironment was prepared, and its drug loading and drug release performance were evaluated. Methods: Based on the MoS2 nanosheets synthesized by hydrothermal method, the S vacant sites of the MoS2 nanosheets were used to connect lipoic acid polyethylene glycol carboxylic acid, which was combined to the Arg-Gly-Asp (RGD) targeting molecule by amide coupling reaction. Succinimidyl 3-[2-pyridyldithio] propionate (SPDP), a linker was then chemically binding to the precedingly prepared composite material, forming the nanocarrier, MoS2-PEG-RGD-SPDP (MPRS). Further, thiolated doxorubicin (DOX) was tethered to the as-prepared nanocarrier, ultimately producing the nanodrug, MPRS-DOX. The synthesized materials were characterized by transmission electron microscope (TEM), X-ray Photoelectron Spectrometer (XPS) and nano-particle potentiometer; The drug loading performance of MPRS was tested by ultraviolet visible spectrophotometer, and the drug releasing performance of MPRS-DOX was investigated by fluorescence spectrophotometer. Results: The MPRS-DOX nanodrug-loading system was successfully synthesized. Its particle size was about 200 nm, and its Zeta potential was +28.2 mV; In addition, its drug-loading efficiency was 86.8%, and its drug-loading amount was 53.5%. In vitro drug release experiments showed that DOX release volume was the highest under the conditions of 10 mM Glutathione (GSH) and pH=5.5. Conclusion: With appropriate particle size, MPRS-DOX nanodrug delivery system is successfully prepared. Furthermore, MPRS-DOX has dual responsiveness of GSH and pH, which can realize the expected controlled drug release in simulated tumor microenvironment. This dual-response nanodrug system of GSH and pH provides a new idea for the construction of a new generation of stimuli-responsive nano-carrier system. |
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