Redox-Responsive Nanogel with Intracellular Reconstruction and Programmable Drug Release for Targeted Tumor Therapy
Redox-Responsive Nanogel with Intracellular Reconstruction and Programmable Drug Release for Targeted Tumor Therapy
复制标题
用于靶向肿瘤治疗的具有细胞内重建和可编程药物释放的氧化还原响应纳米凝胶
DOI：
10.1002/marc.201800824
复制
发表时间：
2019
影响因子：
4.6
通讯作者：
Chen Xin
中科院分区：
文献类型：
--
作者：
Tian Yu;Tian Ran;Li Chen;Jin Ronghua;Feng Yiming;Bai Yongkang;Chen Xin
开发了一种具有氧化还原响应性、大小肿胀和共瞬时药物释放的肿瘤选择性药物传递纳米凝胶。纳米凝胶是由聚乙二醇二缩水甘油醚和半胱胺双交联型透明质酸(HA)形成的。半胱胺中的二硫键(Cys)负责反应，而紧密的聚合物网络使纳米凝胶成为有效载药的胶囊。肿瘤靶向是通过已知的HA受体介导的内吞作用来实现的。在肿瘤靶向和细胞内吞作用后，这种纳米凝胶的响应性肿胀和药物同时释放发生在肿瘤靶向和细胞内吞作用之后，这是由肿瘤细胞胞浆中的大量谷胱甘肽(GSH)触发的。荧光显微镜和流式细胞仪直接证明了肿瘤细胞对纳米凝胶的高选择性摄取。动态光散射和荧光光谱揭示了GSH触发的大小变化和药物的同时释放，导致了更高的肿瘤细胞毒性和比正常细胞高4倍以上的抗肿瘤效果。这些结果表明，这些HA-PEG-Cys-DOX纳米凝胶具有选择性药物传递、细胞内重建和响应性药物释放的性能，有望在癌症治疗中获得更好的疗效。
A tumor‐selective drug delivery nanogel with redox‐responsive size swelling and co‐instantaneous drug release is developed. The nanogel is formed by poly(ethylene glycol) diglycidyl ether and cystamine double crosslinked hyaluronic acid (HA). The disulfide bond in cystamine (Cys) is in charge of the responsiveness, while the compact polymer network turns the nanogel a capsule for effective drug loading. The tumor targeting is achieved by the known HA‐receptor mediated endocytosis. The responsive swelling of this nanogel and co‐instantaneous drug releases happen with the cleavage of the disulfide bond following tumor targeting and cell endocytosis, which is triggered by massive glutathione (GSH) in the cytoplasm of tumor cells. The highly selective nanogel uptake by tumor cells is directly demonstrated by fluorescence microscopy and flow cytometry. The dynamic light scattering and fluorescent spectrum reveal the GSH‐triggered size change and simultaneous drug release, which results in higher tumor cytotoxicity and over fourfold efficacy against tumor cells compared with normal cells. These results indicate that these HA‐PEG‐Cys‐DOX nanogels, with performance of selective drug delivery, intracellular reconstruction, and responsive drug release, are promising platforms for better therapeutic effects in cancer treatment.