Jang Hyung Ha, Park Su Bum, Hong Jeong Sup, Lee Hye Lim, Song Yeon Hui, Kim Jungsoo, Jung Yun Hye, Kim Chan, Kim Doo-Man, Lee Sang Eun, Jeong Young-Il, Kang Dae Hwan
School of Medicine, Pusan National University, Yangsan, Gyeongnam, 50612, South Korea.
Research Institute of Convergence of Biomedical Sciences, Pusan National University Yangsan Hospital, Yangsan, Gyeongnam, 50612, South Korea.
Nanoscale Res Lett. 2019 Feb 18;14(1):58. doi: 10.1186/s11671-019-2887-0.
The aim of this study is to fabricate drug-eluting gastrointestinal (GI) stent using reactive oxygen species (ROS)-sensitive nanofiber mats for treatment of cholangiocarcinoma (CCA) cell. A ROS-producing agent, piperlongumine (PL)-incorporated nanofiber mats were investigated for drug-eluting stent (DES) application.
Selenocystamine-conjugated methoxy poly(ethylene glycol) (MePEG) was conjugated with poly(L-lactide) (PLA) to produce block copolymer (LEse block copolymer). Various ratios of poly(ε-caprolactone) (PCL) and LEse block copolymer were dissolved in organic solvent with PL, and then nanofiber mats were fabricated by electro-spinning techniques.
The higher amount of LEse in the blend of PCL/LEse resulted in the formation of granules while PCL alone showed fine nanofiber structure. Nanofiber mats composed of PCL/LEse polymer blend showed ROS-sensitive drug release, i.e., PL release rate from nanofiber mats was accelerated in the presence of hydrogen peroxide (HO) while nanofiber mats of PCL alone have small changes in drug release rate, indicating that PL-incorporated nanofiber membranes have ROS responsiveness. PL itself and PL released from nanofiber mats showed almost similar anticancer activity against various CCA cells. Furthermore, PL released from nanofiber mats properly produced ROS generation and induced apoptosis of CCA cells as well as PL itself. In HuCC-T1 cell-bearing mice, PL-incorporated nanofiber mats showed improvement in anticancer activity.
PL-incorporated ROS-sensitive nanofiber mats were coated onto GI stent and showed improved anticancer activity with ROS responsiveness. We suggested PL-incorporated ROS-sensitive nanofiber mats as a promising candidate for local treatment of CCA cells.
本研究的目的是使用对活性氧（ROS）敏感的纳米纤维垫制备药物洗脱胃肠道（GI）支架，用于治疗胆管癌（CCA）细胞。研究了一种产生活性氧的试剂——胡椒碱（PL）掺入纳米纤维垫在药物洗脱支架（DES）中的应用。
将硒代胱胺共轭的甲氧基聚（乙二醇）（MePEG）与聚（L-丙交酯）（PLA）共轭以制备嵌段共聚物（LEse嵌段共聚物）。将不同比例的聚（ε-己内酯）（PCL）和LEse嵌段共聚物与PL溶解在有机溶剂中，然后通过静电纺丝技术制备纳米纤维垫。
PCL/LEse共混物中LEse含量较高时会形成颗粒，而单独的PCL呈现出良好的纳米纤维结构。由PCL/LEse聚合物共混物组成的纳米纤维垫表现出对ROS敏感的药物释放，即，在过氧化氢（HO）存在下，纳米纤维垫中PL的释放速率加快，而单独的PCL纳米纤维垫的药物释放速率变化较小，这表明掺入PL的纳米纤维膜具有ROS响应性。PL本身以及从纳米纤维垫释放的PL对各种CCA细胞显示出几乎相似的抗癌活性。此外，从纳米纤维垫释放的PL能适当地产生活性氧并诱导CCA细胞凋亡，与PL本身的作用相同。在携带HuCC-T1细胞的小鼠中，掺入PL的纳米纤维垫显示出抗癌活性的提高。
掺入PL的对ROS敏感的纳米纤维垫被涂覆在GI支架上，并表现出具有ROS响应性的增强抗癌活性。我们认为掺入PL的对ROS敏感的纳米纤维垫是局部治疗CCA细胞的有前途的候选材料。
