Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
Molecules. 2013 Sep 30;18(10):12168-79. doi: 10.3390/molecules181012168.
For the development of effective drug carriers, nanocapsules that respond to micro-environmental changes including a decrease in pH and a reductive environment were prepared by the stabilization of polymer vesicles formed from head-tail type polycations, composed of a polyamidoamine dendron head and a poly(L-lysine) tail (PAMAM dendron-PLL), through the introduction of disulfide bonds between the PLL tails. Disulfide bonds were successfully introduced through the reaction of Lys residues in the PAMAM dendron-PLL polymer vesicles with 2-iminothiolane. The stabilization of PAMAM dendron-PLL polymer vesicles was confirmed by dynamic light scattering measurements. In acid-base titration experiments, nanocapsules cross-linked by disulfide bonds had a buffering effect during the cellular uptake process. The PAMAM dendron-PLL nanocapsules were used to incorporate the fluorescent dyes rhodamine 6G and fluorescein as a drug model. Cationic rhodamine 6G was generally not released from the nanocapsules because of the electrostatic barrier of the PLL membrane. However, the nanocapsules were destabilized at high glutathione concentrations corresponding to intracellular concentrations. Rhodamine 6G was immediately released from the nanocapsules because of destabilization upon the cleavage of disulfide bonds. This release of rhodamine 6G from the nanocapsules was also observed in HeLa cells by laser confocal microscopy.
为了开发有效的药物载体，通过在聚（L-赖氨酸）尾（PLL）之间引入二硫键，制备了对包括 pH 值降低和还原环境在内的微环境变化有响应的纳米胶囊。二硫键是通过 PAMAM 树枝状聚合物囊泡中的 Lys 残基与 2-亚氨基硫烷的反应成功引入的。通过动态光散射测量证实了 PAMAM 树枝状聚合物囊泡的稳定。在酸碱滴定实验中，二硫键交联的纳米胶囊在细胞摄取过程中具有缓冲作用。将荧光染料罗丹明 6G 和荧光素用作药物模型来制备 PAMAM 树枝状聚合物纳米胶囊。由于 PLL 膜的静电势垒，阳离子罗丹明 6G 通常不会从纳米胶囊中释放出来。然而，在对应于细胞内浓度的高谷胱甘肽浓度下，纳米胶囊被破坏。由于二硫键的断裂，罗丹明 6G 立即从纳米胶囊中释放出来。通过激光共聚焦显微镜也观察到罗丹明 6G 从纳米胶囊中的释放。
