A Potential Mechanism of a Cationic Cyclopeptide for Enhancing Insulin Delivery across Caco-2 Cell Monolayers
A Potential Mechanism of a Cationic Cyclopeptide for Enhancing Insulin Delivery across Caco-2 Cell Monolayers
复制标题
阳离子环肽增强跨 Caco-2 细胞单层胰岛素输送的潜在机制
DOI：
10.1248/bpb.b13-00487
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发表时间：
2013-10-01
影响因子：
2
通讯作者：
Wang, Qing
中科院分区：
文献类型：
--
作者：
Chang, Mingming;Li, Xiaohui;Wang, Qing
治疗性生物分子跨生物膜的有效递送是一个具有挑战性的课题。报道了一种名为TD-34（ACSSKKSKHCG）的阳离子环肽，其有效地改善了胰岛素的跨生物膜递送。基于我们以前的工作，我们研究了TD-34促进胰岛素穿过Caco-2细胞单层的机制。在不同条件下，用Caco-2细胞单层分别进行了胰岛素、TD-34和胰岛素与TD-34的转运研究。在转运实验开始后立即监测跨上皮电阻（TEER）值24小时。此外，紧密连接蛋白（Claudin-1）定位通过共聚焦免疫荧光显微镜。结果表明，胰岛素通过生物膜的转运是通过多种途径进行的，包括被动扩散。当TD-34与胰岛素或不与胰岛素共同作用于Caco-2细胞单层时，TEER值可逆地降低，并且与免疫染色检测的紧密连接蛋白的再现相关。结论：阳离子环肽（TD-34）具有通过可逆地松动紧密连接来增强胰岛素跨Caco-2细胞单层的细胞旁递送的潜力。
Effective delivery of therapeutic biomolecules across biomembranes is a challenging topic. A cationic cyclopeptide named TD-34 (ACSSKKSKHCG) was reported to improve insulin delivery across biomembranes effectively. Based on our previous work, we investigated the mechanism of TD-34 for enhancing insulin across Caco-2 cell monolayers. Transport studies of insulin, TD-34 and insulin accompanied with TD-34 were performed respectively using Caco-2 cell monolayers at different conditions. Transepithelial electrical resistance (TEER) value was monitored for 24h immediately after the beginning of transport experiments. Moreover, the tight junction protein (Claudin-1) was localized by confocal immunofluorescence microscopy. Results showed the transport of insulin alone across biomembranes was attributable to multiple routes including passive diffusion. When TD-34 accompanied with or without insulin was treated on Caco-2 cell monolayers, TEER values decreased reversibly, and it was correlated with the reappearance of tight junction proteins by immunostaining assay. It was concluded that the cationic cyclopeptide (TD-34) had the potential to enhance paracellular delivery of insulin across Caco-2 cell monolayers by loosening tight junction reversibly.