Magnetic-Driven Hydrogel Microrobots Selectively Enhance Synthetic Lethality in MTAP-Deleted Osteosarcoma.
Magnetic-Driven Hydrogel Microrobots Selectively Enhance Synthetic Lethality in MTAP-Deleted Osteosarcoma.
复制标题
磁驱动的水凝胶微型机器人选择性地增强了MTAP删除的骨肉瘤中的合成致死性。
DOI：
10.3389/fbioe.2022.911455
复制
发表时间：
2022
影响因子：
5.7
通讯作者：
Hua, Yingqi
中科院分区：
文献类型：
--
作者：
Mu, Haoran;Liu, Chenlu;Zhang, Qi;Meng, Huanliang;Yu, Shimin;Zeng, Ke;Han, Jing;Jin, Xinmeng;Shi, Shi;Yu, Peiyao;Li, Tianlong;Xu, Jing;Hua, Yingqi
背景：基于合成致死性的药物具有抑制肿瘤生长和影响体内正常组织等优点。然而，骨肉瘤的特异性靶点尚未得到确认。在这项研究中，一个非靶向的，但可控的药物输送系统已被应用于选择性地提高骨肉瘤在体外的合成杀伤力，使用磁驱动的水凝胶微型机器人。 方法：本研究选择PRMT 5抑制剂EPZ 015666作为合成致死性药物。然后，载药的水凝胶微机器人含有Fe 3 O 4。利用电子显微镜对微型机器人的形态特征进行了检测。采用CCK-8试剂盒、Western blotting等方法检测体外药物作用，计时显微镜观察微机器人游动情况。在增加的磁场中通过培养的肿瘤验证选择性抑制。 结果如下：MTAP缺失突变在TCGA数据库中的泛癌（近10.00%）和TARGET数据库中的骨肉瘤（23.86%）中常见。根据CCLE数据库和RT-PCR检测HOS及其衍生物143 B和HOS/MNNG的MTAP缺失。PRMT 5抑制剂EPZ 015666可降低143 B和HOS/MNNG的SDMA修饰和肿瘤生长抑制。合成了水凝胶微机器人给药系统，并对药物进行了罗丹明染色。微型机器人由磁场驱动。进行微机器人的选择性抑制的模拟，并且通过添加高剂量的微机器人检测到肿瘤细胞的较低细胞活力。 结论：磁驱动给药系统可以携带合成的杀伤性药物。同时，该体系的选择性抑制可以通过编程控制磁场强度来实现。
Background: Drugs based on synthetic lethality have advantages such as inhibiting tumor growth and affecting normal tissue in vivo. However, specific targets for osteosarcoma have not been acknowledged yet. In this study, a non-targeted but controllable drug delivery system has been applied to selectively enhance synthetic lethality in osteosarcoma in vitro, using the magnetic-driven hydrogel microrobots. Methods: In this study, EPZ015666, a PRMT5 inhibitor, was selected as the synthetic lethality drug. Then, the drug was carried by hydrogel microrobots containing Fe3O4. Morphological characteristics of the microrobots were detected using electron microscopy. In vitro drug effect was detected by the CCK-8 assay kit, Western blotting, etc. Swimming of microrobots was observed by a timing microscope. Selective inhibition was verified by cultured tumors in an increasing magnetic field. Results: Genomic mutation of MTAP deletion occurred commonly in pan-cancer in the TCGA database (nearly 10.00%) and in osteosarcoma in the TARGET database (23.86%). HOS and its derivatives, 143B and HOS/MNNG, were detected by MTAP deletion according to the CCLE database and RT-PCR. EPZ015666, the PRMT5 inhibitor, could reduce the SDMA modification and inhibition of tumor growth of 143B and HOS/MNNG. The hydrogel microrobot drug delivery system was synthesized, and the drug was stained by rhodamine. The microrobots were powered actively by a magnetic field. A simulation of the selected inhibition of microrobots was performed and lower cell viability of tumor cells was detected by adding a high dose of microrobots. Conclusion: Our magnetic-driven drug delivery system could carry synthetic lethality drugs. Meanwhile, the selective inhibition of this system could be easily controlled by programming the strength of the magnetic field.
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DOI：
10.1016/j.mtbio.2020.100085
发表时间：
2020-09
期刊：
Materials today. Bio
影响因子：
--
作者：
Koleoso M;Feng X;Xue Y;Li Q;Munshi T;Chen X
通讯作者：
Chen X
影响因子：
10.8
作者：
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通讯作者：
Wang, Joseph
影响因子：
10.8
作者：
Li, Tianlong;Li, Jinxing;Wang, Joseph
通讯作者：
Wang, Joseph
影响因子：
4.1
作者：
Mu, Guanyu;Zhao, Jie;Sun, Tong
通讯作者：
Sun, Tong
高效光驱动 TiO2-Au Janus 微电机
影响因子：
17.1
作者：
Dong, Renfeng;Zhang, Qilu;Ren, Biye
通讯作者：
Ren, Biye