FRET imaging reveals different cellular entry routes of self-assembled and disulfide bonded polymeric micelles.-猫眼课题宝

DOI：

10.1021/mp4003333

发表时间：

2013-09-03

期刊：

Molecular pharmaceutics

影响因子：

4.9

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

Lee SY;Tyler JY;Kim S;Park K;Cheng JX

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946486/?report=classic

虽然纳米载体有望用于癌症化疗，但其细胞内药物传递途径尚未完全了解。特别是，纳米载体的稳定性对细胞摄取的影响仍不确定。通过物理加载疏水性FRET探针，我们揭示了自组装和二硫键胶束的不同细胞内药物递送途径。自组装胶束通过胶束-膜相互作用在结构上解离，疏水探针分布在质膜上。或者，携带疏水探针的完整二硫键胶束通过多种内吞途径内化到癌细胞中。内化后，通过谷胱甘肽介导的二硫键还原，在早期核内体中分解二硫键胶束，使探针暴露于细胞内细胞器。

Although nanocarriers hold promise for cancer chemotherapy, their intracellular drug delivery pathways are not fully understood. In particular, the influence of nanocarrier stability on cellular uptake is still uncertain. By physically loading hydrophobic FRET probes, we revealed different intracellular drug delivery routes of self-assembled and disulfide bonded micelles. The self-assembled micelles were structurally dissociated by micelle-membrane interactions, and the hydrophobic probes were distributed on the plasma membrane. Alternatively, intact disulfide bonded micelles carrying hydrophobic probes were internalized into cancer cells via multiple endocytic pathways. Following internalization, disulfide bonded micelles were decomposed in early endosomes by glutathione-mediated disulfide bond reduction, exposing the probes to intracellular organelles.