A Mitochondria‐Targeting Gold–Peptide Nanoassembly for Enhanced Cancer‐Cell Killing
A Mitochondria‐Targeting Gold–Peptide Nanoassembly for Enhanced Cancer‐Cell Killing
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DOI：
10.1002/adhm.201300037
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发表时间：
2013-12
影响因子：
10
通讯作者：
Xiaochuan Ma;Xiaobo Wang;Ming Zhou;H. Fei
中科院分区：
文献类型：
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作者：
Xiaochuan Ma;Xiaobo Wang;Ming Zhou;H. Fei
用于有效递送和治疗应用的多功能纳米颗粒的设计和构建仍然是一项具有挑战性的任务。人们希望纳米颗粒能够克服多重生物屏障并到达特定的细胞位置以实现最大的治疗效果。这一目标通常需要微调纳米颗粒的化学和物理特性，以及更好地了解它们与活细胞的相互作用。设计了肽修饰的金纳米颗粒平台，该平台由一个 20 nm 金核心组成，该核心由一层生物素化的 CALNN 肽稳定，另一层是四聚体链霉亲和素，用于用生物素化分子进行功能化。纳米组装体经历了有效的动力依赖和小凹介导的内吞途径，并显示出对线粒体（具有重要治疗意义的细胞器）的高度特异性定位。当用细胞毒性肽 (KLA: (KLAKLAK)2) 进行功能化时，KLA 锚定的纳米组件表现出显着增强的抗癌活性，比游离 KLA 肽强数千倍，这可能是因为它提高了细胞进入效率、线粒体特异性递送以及纳米组件的多价效应。该研究开辟了开发线粒体靶向纳米药物的可能性。
Design and construction of multifunctional nanoparticles for effective delivery and therapeutic application remains a challenging task. It is desirable that nanoparticles can overcome multiple biological barriers and reach specific cellular locations to achieve maximum therapeutic effects. This aim often requires the fine tuning of nanoparticles' chemical and physical properties, as well as better understanding of their interaction with live cells. A peptide‐modified gold–nanoparticle platform is designed, which consists of a 20‐nm gold core stabilized with a layer of biotinylated CALNN‐based peptides and a further layer of tetrameric streptavidins for functionalization with biotinylated molecules. The nanoassembly undergoes an efficient dynamin‐dependent and caveolae‐mediated endocytosis pathway, and displays highly specific localization to mitochondria, organelles of great therapeutic importance. When functionalized with a cytotoxic peptide (KLA: (KLAKLAK)2), the KLA‐anchored nanoassembly exhibits dramatically enhanced anticancer activity, thousands of times stronger than that of the free KLA peptide, likely because of its improved cell entry efficiency, mitochondria‐specific delivery, and the polyvalent effect of the nanoassembly. The study opens up the possibility of developing mitochondria‐targeted nanomedicines.