用于肺转移性骨肉瘤治疗的VEGFR2 siRNA封装小型细胞外泡泡的体内自组装和传递。
In vivo self-assembly and delivery of VEGFR2 siRNA-encapsulated small extracellular vesicles for lung metastatic osteosarcoma therapy.
发表日期：2023 Sep 22
作者：
Lingfeng Yu, Gentao Fan, Qingyan Wang, Yan Zhu, Hao Zhu, Jiang Chang, Zhen Wang, Shoubin Zhan, Xianming Hua, Diankun She, Jianhao Huang, Yicun Wang, Jianning Zhao, Chen-Yu Zhang, Xi Chen, Guangxin Zhou
来源：
Cell Death & Disease
摘要：
肺转移性骨肉瘤（OS）的预后仍然令人失望。基于siRNA的VEGFR2基因沉默是治疗肺转移性OS的一种有希望的策略，但缺乏安全高效的递送系统用于包裹siRNA进行体内给药。本研究提出了一种合成生物学策略，通过合成遗传电路来改造宿主肝脏，以实现高效体内VEGFR2 siRNA递送。在被肝细胞摄取后，遗传电路（以DNA质粒的形式）重编程肝脏，驱动自主肝内组装和包封VEGFR2 siRNA进入分泌性小胞体（sEVs），从而实现VEGFR2 siRNA自组装向肺部的转运。结果表明，相比于肺转移性OS的正性药物（阿帕替尼），我们的策略在治疗功效和毒副作用方面更具优势，可以为肺转移性OS提供可行且可行的治疗方案。© 2023年。作者（们）。
The prognosis of lung metastatic osteosarcoma (OS) remains disappointing. siRNA-based gene silencing of VEGFR2 is a promising treatment strategy for lung metastatic OS, but there is a lack of safe and efficient delivery systems to encapsulate siRNAs for in vivo administration. This study presented a synthetic biological strategy that remolds the host liver with synthesized genetic circuits for efficient in vivo VEGFR2 siRNA delivery. After being taken-up by hepatocytes, the genetic circuit (in the form of a DNA plasmid) reprogrammed the liver to drive the autonomous intrahepatic assembly and encapsulation of VEGFR2 siRNAs into secretory small extracellular vesicles (sEVs), thus allowing for the transport of self-assembled VEGFR2 siRNAs towards the lung. The results showed that our strategy was superior to the positive medicine (Apatinib) for OS lung metastasis in terms of therapeutic efficacy and toxic adverse effects and may provide a feasible and viable therapeutic solution for lung metastatic OS.© 2023. The Author(s).