Role of Endosomal Escape for Disulfide-Based Drug Delivery from Colloidal Mesoporous Silica Evaluated by Live-Cell Imaging
Role of Endosomal Escape for Disulfide-Based Drug Delivery from Colloidal Mesoporous Silica Evaluated by Live-Cell Imaging
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DOI：
10.1021/nl102180s
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发表时间：
2010-09-01
期刊：
影响因子：
10.8
通讯作者：
Braeuchle, Christoph
中科院分区：
文献类型：
--
作者：
Sauer, Anna M.;Schlossbauer, Axel;Braeuchle, Christoph
氧化还原驱动的细胞内二硫键裂解是实现刺激响应和药物控制释放的有前途的策略。我们合成了具有ATTO 633标记的半胱氨酸通过二硫桥连接到内部颗粒核心的胶体介孔二氧化硅（CMS）纳米颗粒，并通过高分辨率荧光显微镜表征了内化到HuH7细胞后的半胱氨酸释放行为。我们的研究表明，内体逃逸是基于二硫键的药物释放的瓶颈。内体的光化学打开导致荧光标记的半胱氨酸成功递送至胞质溶胶。
Redox-driven intracellular disulfide-cleavage is a promising strategy to achieve stimuli-responsive and controlled drug release. We synthesized colloidal mesoporous silica (CMS) nanoparticles with ATTO633-labeled cysteine linked to the inner particle core via disulfide-bridges and characterized their cysteine release behavior after internalization into HuH7 cells by high-resolution fluorescence microscopy. Our study revealed that endosomal escape is a bottleneck for disulfide-linkage based drug release. Photochemical opening of the endosome leads to successful delivery of fluorescently labeled cysteine to the cytosol.