Department of Chemistry and Center for Nanoscience, University of Munich LMU, Butenandtstrasse 11, Gerhardt-Ertl-Building, 81377 Munich, Germany.
Nano Lett. 2010 Sep 8;10(9):3684-91. doi: 10.1021/nl102180s.
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.
氧化还原驱动的细胞内二硫键断裂是一种很有前途的策略，可以实现刺激响应和控制药物释放。我们合成了胶体介孔硅（CMS）纳米粒子，其内部颗粒核心通过二硫键连接有 ATTO633 标记的半胱氨酸，并通过高分辨率荧光显微镜研究了它们内化进入 HuH7 细胞后的半胱氨酸释放行为。我们的研究表明，内涵体逃逸是基于二硫键的药物释放的一个瓶颈。内涵体的光化学打开导致荧光标记的半胱氨酸成功递送到细胞质中。
