Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery
Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery
复制标题
谷胱甘肽响应纳米载体作为靶向细胞内药物和基因递送的有前途的平台
DOI：
10.1016/j.jconrel.2011.01.030
复制
发表时间：
2011-05-30
影响因子：
10.8
通讯作者：
Zhong, Zhiyuan
中科院分区：
文献类型：
--
作者：
Cheng, Ru;Feng, Fang;Zhong, Zhiyuan
在过去的几年里，在用于靶向细胞内药物和基因递送的谷胱甘肽响应性纳米载体的开发方面取得了巨大的进展，这是由于以下事实的驱动：(I)许多治疗药物(例如抗癌药物、光敏剂和抗氧化剂)和生物治疗药物(例如多肽和蛋白质药物以及siRNA)仅在像胞浆和细胞核这样的细胞内发挥治疗作用，以及(Ii)像胞浆、线粒体和细胞核这样的几个细胞内隔室含有高浓度的谷胱甘肽(GSH)三肽(约2-10 mM)，这是胞外液和循环中的100-1000倍(约2-20微米)。谷胱甘肽被认为是一种理想的、普遍存在的内刺激物质，可以使纳米载体在细胞内快速失稳，从而实现高效的细胞内药物释放。在本文中，我们将综述GSH响应性纳米载体的最新研究成果，特别是胶束、纳米粒子、胶囊、聚合物、纳米凝胶、树枝状药物和大分子药物结合物，以及用于控制传递抗癌药物(如阿霉素和紫杉醇)、光敏剂、抗氧化剂、多肽、蛋白质药物和核酸(如DNA、siRNA和反义寡核苷酸)的纳米核酸复合体。独特的二硫化物化学使多功能递送系统的新颖和多功能设计成为可能，解决了细胞内和细胞外的障碍。我们相信，GSH响应型纳米载体系统在肿瘤靶向治疗方面具有巨大的潜力。(C)2011爱思唯尔B.V.保留所有权利。
The past couple of years have witnessed a tremendous progress in the development of glutathione-responsive nano-vehicles for targeted intracellular drug and gene delivery, as driven by the facts that (i) many therapeutics (e.g. anti-cancer drugs, photosensitizers, and anti-oxidants) and biotherapeutics (e.g. peptide and protein drugs, and siRNA) exert therapeutical effects only inside cells like the cytosol and cell nucleus, and (ii) several intracellular compartments such as cytosol, mitochondria, and cell nucleus contain a high concentration of glutathione (GSH) tripeptides (about 2-10 mM), which is 100 to 1000 times higher than that in the extracellular fluids and circulation (about 2-20 mu M). Glutathione has been recognized as an ideal and ubiquitous internal stimulus for rapid destabilization of nano-carriers inside cells to accomplish efficient intracellular drug release. In this paper, we will review recent results on GSH-responsive nano-vehicles in particular micelles, nanoparticles, capsules, polymersomes, nanogels, dendritic and macromolecular drug conjugates, and nano-sized nucleic acid complexes for controlled delivery of anti-cancer drugs (e.g. doxorubicin and paclitaxel), photosensitizers, anti-oxidants, peptides, protein drugs, and nucleic acids (e.g. DNA, siRNA, and antisense oligodeoxynucleotide). The unique disulfide chemistry has enabled novel and versatile designs of multifunctional delivery systems addressing both intracellular and extracellular barriers. We are convinced that GSH-responsive nano-carrier systems have enormous potential in targeted cancer therapy. (C) 2011 Elsevier B.V. All rights reserved.