| 赵 勇,郭晨博,吴朋朋,秦 靖,白 冰,师长宏.双模态纳米诊疗一体药物在肝癌动物模型中的应用[J].,2023,(19):3614-3618 |
| 双模态纳米诊疗一体药物在肝癌动物模型中的应用 |
| Application of Dual-mode Nano Medicine for Diagnosis and Treatment in Animal Models of Liver Cancer |
| 投稿时间：2023-03-26 修订日期：2023-04-30 |
| DOI：10.13241/j.cnki.pmb.2023.19.003 |
| 中文关键词: 纳米粒子 诊疗一体化 肝癌 肿瘤 |
| 英文关键词: Nanoparticles Integration of diagnosis and treatment Liver cancer Tumor |
| 基金项目:陕西省创新能力支撑计划项目（2021PT-054；2022PT-36）；军队实验动物专项课题（SYDW【2018】08） |
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| 中文摘要: |
| 摘要 目的：构建一种肿瘤诊断和治疗一体化药物，并利用肝癌动物模型开展诊疗效能评价。方法：利用多孔金属有机骨架材料ZIF-8，通过配位作用同时对化疗药物阿霉素（DOX）和近红外荧光染料IR-820进行负载。而后，利用超声的方法在ZIF-8-IR-820-DOX表面修饰了红细胞膜以提高载药体系的生物安全性和稳定性，得到具有生物伪装特性的pH响应型ZIF-8-IR-820-DOX@RM纳米颗粒。最后，通过对该药物体系的粒径、表面电位、形貌等理化性质进行表征，并利用肝癌动物模型验证该药物的诊断和治疗效能。结果：成功构建了一款红细胞伪装的金属框架纳米诊疗一体试剂，该试剂具有较好的pH相应性，在肿瘤pH 5.5 条件下，药物的释放率达到98.4 %，而在机体正常pH 7.4条件下，释放率仅为15.3 %。在小鼠肝癌动物模型的诊疗过程中，能通过近红外荧光较好的识别肿瘤的位置和大小，且对小鼠肿瘤具有较好的治疗效果。结论：本研究所构建的ZIF-8-IR-820-DOX @RM能通过肿瘤处增强的渗透性和保留（EPR）效应，精准的到达肿瘤部位，并利用pH响应性，在肿瘤酸性环境中精准释放携带的抗肿瘤药物和近红外荧光成像试剂，实现对肿瘤的诊断和治疗一体化设计。为肿瘤治疗的相关研究提供了一种思路和借鉴。 |
| 英文摘要: |
| ABSTRACT Objective: To construct an integrated drug for tumor diagnosis and treatment, and to evaluate the efficacy of diagnosis and treatment by using animal model of liver cancer. Methods: A porous metal-organic skeleton material, ZIF-8, was synthesized by chemical methods and loaded with doxorubicin (DOX) and near-infrared fluorescent dye (IR-820) by coordination. Then, the erythrocyte membrane was modified on the surface of ZIF-8-IR-820-DOX by ultrasonic method to improve the biosafety and stability of the drug delivery system, and the biological camouflage characteristics of ZIF-8-DOX-IR-820@RM was obtained. Finally, the particle size, surface potential, morphology and other physicochemical properties of the drug system were characterized, and the diagnosis and therapeutic efficacy of the drug was verified by the animal model of liver cancer. Results: A metal frame nano diagnostic reagent disguised with red blood cells was successfully constructed. The reagent has good pH response, and the drug release rate reached 98.4 % under the condition of tumor pH5.5, but only 15.3 % under the condition of normal body pH7.4. In the diagnosis and treatment process of mouse liver cancer animal model, the near infrared fluorescence can better identify the location and size of the tumor, and has a good therapeutic effect on the mouse tumor. Conclusion: The ZIF-8 -IR-820-DOX @RM constructed in this study can accurately reach the tumor site through the enhanced permeability and retention (EPR) effect at the tumor site, and use pH responsiveness to accurately release the anti-tumor drugs and near-infrared fluorescence imaging reagents carried in the acidic environment of the tumor, so as to realize the integrated design of tumor diagnosis and treatment. It provides a kind of thought and reference for the related research of tumor treatment. |
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