N-acetyl histidine-conjugated glycol chitosan self-assembled nanoparticles for intracytoplasmic delivery of drugs:: Endocytosis, exocytosis and drug release
N-acetyl histidine-conjugated glycol chitosan self-assembled nanoparticles for intracytoplasmic delivery of drugs:: Endocytosis, exocytosis and drug release
复制标题
DOI：
10.1016/j.jconrel.2006.07.011
复制
发表时间：
2006-09-28
影响因子：
10.8
通讯作者：
Cho, Yong Woo
中科院分区：
文献类型：
--
作者：
Park, Ji Sun;Han, Tae Hee;Cho, Yong Woo
纳米尺寸的囊泡系统（纳米颗粒），尺寸范围从10 nm至1000 nm，具有作为药物递送系统的潜在应用。成功的临床应用需要载药纳米颗粒的有效细胞内递送。在这里，我们描述了N-乙酰基组氨酸共轭乙二醇壳聚糖（NAcHis-GC）自组装纳米粒子作为一个有前途的系统胞浆内药物输送。由于N-乙酰基组氨酸（NAcHis）在中性pH下是疏水性的，缀合物形成平均直径为150-250 nm的自组装纳米颗粒。在微酸性环境中，例如在核内体中，由于NAcHis的咪唑基团的质子化破坏了亲水/疏水平衡，纳米颗粒被分解。通过流式细胞仪和共聚焦显微镜研究了pH敏感性自组装纳米颗粒的细胞内化和药物释放。通过吸附性内吞作用内化的NAcHis-GC纳米颗粒被胞吐或定位于内体中。胞吐的纳米颗粒的量取决于从培养基中去除游离纳米颗粒之前的预孵育时间。流式细胞术和共聚焦显微镜显示NAcHis-GC纳米颗粒将药物释放到胞质溶胶中，细胞周期分析表明，紫杉醇掺入的NAcHis-GC纳米颗粒可有效诱导细胞生长停滞。(c)2006 Elsevier B. V.保留所有权利。
Nano-sized vesicular systems (nanoparticles), ranging from 10 nm to 1000 nm in size, have potential applications as drug delivery systems. Successful clinical applications require the efficient intracellular delivery of drug-loaded nanoparticles. Here we describe N-acetyl histidine-conjugated glycol chitosan (NAcHis-GC) self-assembled nanoparticles as a promising system for intracytoplasmic delivery of drugs. Because N-acetyl histidine (NAcHis) is hydrophobic at neutral pH, the conjugates formed self-assembled nanoparticles with mean diameters of 150-250 nm. In slightly acidic environments, such as those in endosomes, the nanoparticles were disassembled due to breakdown of the hydrophilic/hydrophobic balance by the protonation of the imidazole group of NAcHis. Cellular internalization and drug release of the pH-sensitive self-assembled nanoparticles were investigated by flow cytometry and confocal microscopy. NAcHis-GC nanoparticles internalized by adsorptive endocytosis were exocytosed or localized in endosomes. The amount of exocytosed nanoparticles was dependent on the pre-incubation time prior to removal of free nanoparticles from the culture media. Flow cytometry and confocal microscopy showed that NAcHis-GC nanoparticles released drugs into the cytosol and cell cycle analysis demonstrated that paclitaxel-incorporated NAcHis-GC nanoparticles were effective in inducing arrest of cell growth. (c) 2006 Elsevier B.V. All rights reserved.