National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, 610064, PR China.
Small. 2014 Mar 26;10(6):1133-40. doi: 10.1002/smll.201301885. Epub 2013 Oct 24.
A novel type of nanovehicle (NV) based on stimuli-responsive supramolecular peptide-amphiphiles (SPAs, dendritic poly (L-lysine) non-covalently linked poly (L-leucine)) is developed for intracellular drug delivery. To determine the pH-dependent mechanism, the supramolecular peptide-amphiphile system (SPAS) is investigated at different pH conditions using a variety of physical and chemical approaches. The pH-triggered disassembly of SPAS can be attributed to the disappearance of non-covalent interactions within SPAs around the isoelectric point of poly (L-leucine). SPAS is found to encapsulate guest molecules at pH 7.4 but release them at pH 6.2. In this way, SPAS is able to act as a smart NV to deliver its target to tumor cells using intracellular pH as a trigger. The DOX-loaded NVs are approximately 150 nm in size. In vitro release profiles and confocal laser scanning microscopy (CLSM) images of HepG2 cells confirm that lower pH conditions can trigger the disassembly of NVs and so achieve pH-dependent intracellular DOX delivery. In vitro cytotoxicity of the DOX-loaded NVs to HepG2 cells demonstrate that the smart NVs enhance the efficacy of hydrophobic DOX. Fluorescence-activated cell sorting (FACS) and CLSM results show that the NVs can enhance the endocytosis of DOX into HepG2 cells considerably and deliver DOX to the nuclei.
一种基于刺激响应超分子肽两亲体（SPAs，树枝状多聚（L-赖氨酸）非共价连接多聚（L-亮氨酸））的新型纳米载体（NV）被开发用于细胞内药物递送。为了确定 pH 依赖性机制，使用各种物理和化学方法在不同 pH 条件下研究了超分子肽两亲体系统（SPAS）。SPAS 的 pH 触发解组装可以归因于聚（L-亮氨酸）等电点周围 SPAS 内的非共价相互作用的消失。发现 SPAS 在 pH 7.4 时可以包封客体分子，但在 pH 6.2 时释放它们。通过这种方式，SPAS 能够作为一种智能 NV，利用细胞内 pH 作为触发因素将其靶标递送到肿瘤细胞中。负载 DOX 的 NV 的尺寸约为 150nm。HepG2 细胞的体外释放曲线和共焦激光扫描显微镜（CLSM）图像证实，较低的 pH 条件可以触发 NV 的解组装，从而实现 pH 依赖性的细胞内 DOX 递药。负载 DOX 的 NV 对 HepG2 细胞的体外细胞毒性表明，智能 NV 增强了疏水性 DOX 的功效。荧光激活细胞分选（FACS）和 CLSM 结果表明，NV 可以大大增强 DOX 进入 HepG2 细胞的内吞作用，并将 DOX 递送至细胞核。
