Direct proof of spontaneous translocation of lipid-covered hydrophobic nanoparticles through a phospholipid bilayer.
Direct proof of spontaneous translocation of lipid-covered hydrophobic nanoparticles through a phospholipid bilayer.
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DOI：
10.1126/sciadv.1600261
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发表时间：
2016-11
期刊：
影响因子：
13.6
通讯作者：
Baulin VA
中科院分区：
文献类型：
--
作者：
Guo Y;Terazzi E;Seemann R;Fleury JB;Baulin VA
自发易位脂质包被的疏水金纳米粒子为新的生物技术应用打开了大门。引入到生命系统中的疏水纳米颗粒可能导致毒性增加，可以激活免疫细胞，或者可以用作药物或基因递送的纳米载体。通常认为，小的疏水纳米颗粒被脂质双层阻挡并积聚在双层核心中，而大的纳米颗粒只能通过缓慢的能量依赖性过程（例如持续数分钟的内吞作用）穿透细胞。与预期相反，我们证明了脂质覆盖的疏水纳米颗粒可以在毫秒内通过直接渗透穿过脂质膜。我们确定了易位的阈值尺寸：直径小于5 nm的纳米颗粒被困在双层中，而直径大于5 nm的纳米颗粒插入双层中，打开双层中的孔。通过原位观察纳米颗粒离开双层的单一事件提供了这种尺寸依赖性易位的直接证据。这是实现了一个专门设计的微流控装置相结合的光学荧光显微镜，同时电生理测量。对单个纳米颗粒易位事件的动力学途径的定量分析表明，易位是不可逆的，并且纳米颗粒只能易位一次。这种新发现的单向易位机制为生物技术应用提供了许多机会，从靶向生物材料消除和/或递送到精确和受控的纳米颗粒捕获。
Spontaneously translocating lipid-coated hydrophobic gold nanoparticles open doors for new biotechnology applications. Hydrophobic nanoparticles introduced into living systems may lead to increased toxicity, can activate immune cells, or can be used as nanocarriers for drug or gene delivery. It is generally accepted that small hydrophobic nanoparticles are blocked by lipid bilayers and accumulate in the bilayer core, whereas big nanoparticles can only penetrate cells through slow energy-dependent processes, such as endocytosis, lasting minutes. In contrast to expectations, we demonstrate that lipid-covered hydrophobic nanoparticles may translocate through lipid membranes by direct penetration within milliseconds. We identified the threshold size for translocation: nanoparticles with diameters smaller than 5 nm stay trapped in the bilayer, whereas those with diameters larger than 5 nm insert into the bilayer, opening pores in the bilayer. The direct proof of this size-dependent translocation was provided by an in situ observation of a single event of a nanoparticle quitting the bilayer. This was achieved with a specially designed microfluidic device combining optical fluorescence microscopy with simultaneous electrophysiological measurements. A quantitative analysis of the kinetic pathway of a single nanoparticle translocation event demonstrated that the translocation is irreversible and that the nanoparticle can translocate only once. This newly discovered one-way translocation mechanism provides numerous opportunities for biotechnological applications, ranging from targeted biomaterial elimination and/or delivery to precise and controlled trapping of nanoparticles.
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