Lee Seung-Young, Tyler Jacqueline Y, Kim Sungwon, Park Kinam, Cheng Ji-Xin
Weldon School of Biomedical Engineering, ‡Department of Industrial and Physical Pharmacy, and §Department of Chemistry, Purdue University , West Lafayette, Indiana 47907, United States.
Mol Pharm. 2013 Sep 3;10(9):3497-506. doi: 10.1021/mp4003333. Epub 2013 Aug 15.
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.
尽管纳米载体在癌症化疗方面具有前景，但其细胞内药物递送途径尚未完全明确。特别是，纳米载体稳定性对细胞摄取的影响仍不确定。通过物理装载疏水性荧光共振能量转移（FRET）探针，我们揭示了自组装和二硫键连接的胶束不同的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，疏水性探针分布在质膜上。相反，携带疏水性探针的完整二硫键连接胶束通过多种内吞途径内化到癌细胞中。内化后，二硫键连接的胶束在早期内体中通过谷胱甘肽介导的二硫键还原而分解，使探针暴露于细胞内细胞器。
