Intracellular delivery of quantum dots mediated by a histidine- and arginine-rich HR9 cell-penetrating peptide through the direct membrane translocation mechanism
Intracellular delivery of quantum dots mediated by a histidine- and arginine-rich HR9 cell-penetrating peptide through the direct membrane translocation mechanism
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DOI：
10.1016/j.biomaterials.2011.01.041
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发表时间：
2011-05-01
期刊：
影响因子：
14
通讯作者：
Lee, Han-Jung
中科院分区：
文献类型：
--
作者：
Liu, Betty R.;Huang, Yue-wern;Lee, Han-Jung
近年来，在生物材料研究中，已开发出将半导体量子点（QD）等生物材料转移到细胞中的功能性肽。由于溶酶体捕获，通过内吞途径将与细胞穿透肽（CPP）缀合的量子点递送到细胞中在生物医学应用中存在问题。在这里，我们证明富含组氨酸和精氨酸的 CPP（HR9 肽）与 QD 稳定且非共价结合，能够在极短的时间内（4 分钟）进入细胞。中断F-肌动蛋白聚合和主动转运并不能抑制HR9/QD复合物进入细胞，表明HR9直接穿透细胞膜。亚细胞共定位研究表明，HR9 递送的量子点停留在细胞质中，没有任何细胞器捕获。二甲基亚砜、乙醇和油酸（但不是芘丁酸）通过促进直接膜易位途径增强了 HR9 介导的 QD 细胞内递送。 HR9 和 HR9/QD 没有细胞毒性。这些发现表明 HR9 可能是一种有效的载体，可以在不干扰药物治疗活性的情况下递送药物。 (C) 2011 Elsevier Ltd. 保留所有权利。
Functional peptides that transfer biomaterials, such as semiconductor quantum dots (QDs), into cells in biomaterial research have been developed in recent years. Delivery of QDs conjugated with cell-penetrating peptides (CPPs) into cells by the endocytic pathway was problematic in biomedical applications because of lysosomal trapping. Here, we demonstrate that histidine- and arginine-rich CPPs (HR9 peptides) stably and noncovalently combined with QDs are able to enter into cells in an extremely short period (4 min). Interrupting both F-actin polymerization and active transport did not inhibit the entry of HR9/QD complexes into cells, indicating that HR9 penetrates cell membrane directly. Subcellular colocalization studies indicated that QDs delivered by HR9 stay in cytosol without any organelle capture. Dimethyl sulphoxide, ethanol and oleic acid, but not pyrenebutyrate, enhanced HR9-mediated intracellular delivery of QDs by promoting the direct membrane translocation pathway. HR9 and HR9/QDs were not cytotoxic. These findings suggest that HR9 could be an efficient carrier to deliver drugs without interfering with their therapeutic activity. (C) 2011 Elsevier Ltd. All rights reserved.