Hijacking Self-Assembly to Establish Intracellular Functional Nanoparticles.
Hijacking Self-Assembly to Establish Intracellular Functional Nanoparticles.
复制标题
劫持自组装建立细胞内功能纳米颗粒
DOI：
10.1002/advs.202203027
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发表时间：
2022-11
期刊：
影响因子：
15.1
通讯作者：
Wu, Jinhui
中科院分区：
文献类型：
--
作者：
Liu, Yang;Wang, Yuchen;Wang, Chao;Dong, Tiejun;Xu, Haiheng;Guo, Yunfei;Zhao, Xiaozhi;Hu, Yiqiao;Wu, Jinhui
关键词：
纳米药物的靶向运输经常受到体内各种生物事件的阻碍。病毒可以劫持宿主细胞并利用细胞内转录和翻译生物事件来实现其复制。受此启发，建立了劫持生物事件的内源性产物组装成细胞内功能性纳米颗粒的策略。研究表明，在肿瘤血管破坏治疗后，注射的细胞渗透性小分子药物双膦酸盐可以劫持出血产物铁，并在肿瘤浸润性巨噬细胞内自组装成过氧化物酶样纳米颗粒。与游离药物不同，产生的细胞间纳米颗粒可以特异性地对线粒体施加压力，导致体外巨噬细胞的免疫激活，并将肿瘤相关巨噬细胞（TAMs）从免疫抑制极化为杀肿瘤，并增加肿瘤深处T细胞的募集。与单独使用血管破坏剂的治疗相比，劫持自组装策略显著抑制了肿瘤生长。利用双膦酸盐劫持与出血相关的代谢产物铁，在特定细胞内制造功能性纳米颗粒，这可能为药物递送和小分子药物开发开辟新的纳米技术。全身注射的小分子药物双膦酸盐与内源性亚铁（红细胞降解的产物）反应，最终自组装成功能性纳米颗粒以调节细胞的行为。这种受病毒启发的劫持自组装策略为小分子药物的细胞靶向和作用模式带来了新的临床可行的纳米技术。
The targeted transport of nanomedicines is often impeded by various biological events in the body. Viruses can hijack host cells and utilize intracellular transcription and translation biological events to achieve their replication. Inspired by this, a strategy to hijack endogenous products of biological events to assemble into intracellular functional nanoparticles is established. It has been shown that, following tumor vessel destruction therapy, injected cell permeable small molecule drugs bisphosphonate can hijack the hemorrhagic product iron and self‐assemble into peroxidase‐like nanoparticles within tumor‐infiltrating macrophages. Unlike free drugs, the generated intercellular nanoparticles can specifically stress mitochondria, resulting in immune activation of macrophages in vitro and polarizing tumor‐associated macrophages (TAMs) from immunosuppressive to tumoricidal and increasing the recruitment of T cells deep within tumor. The hijacking self‐assembly strategy significantly inhibits tumor growth compared with the treatment of vascular‐disrupting agents alone. Using bisphosphonate to hijack the metabolite associated with hemorrhage, iron, to fabricate functional nanoparticles within specific cells, which may open up new nanotechnology for drug delivery and small molecular drug development. Systemically injected small molecule agents bisphosphonate react with endogenous ferrous iron, the product of erythrocyte degradation, and finally self‐assembly into functional nanoparticles to regulate the behavior of cells. This virus‐inspired hijacking self‐assembly strategy brings new clinically feasible nanotechnology for the cell targeting and action mode of small molecule agents.
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