Miao Jing, Zhang Liwen, Gao Peng, Zhao Huawei, Xie Xianji, Wang Junyan
Department of Pharmacy, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China.
Department of Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Polymers (Basel). 2021 Aug 30;13(17):2929. doi: 10.3390/polym13172929.
Glucose Transporter-1 (GLUT-1) is considered to be a possible intrinsic marker of hypoxia in malignant tumors, which is an important factor in radioresistance of laryngocarcinoma. We speculated that the inhibition of GLUT-1 expression might improve the radiosensitivity of laryngocarcinoma. GLUT-1 siRNA was designed to inhibit the GLUT-1 expression, but the high molecular weight and difficult drug delivery limited the application. Herein, we constructed a glycolipid polymer chitosan oligosaccharide grafted stearic acid (CSSA) to conjugate siRNA via electrostatic interaction. The characteristics of CSSA and CSSA/siRNA were studied, as well as the radiosensitization effect of siRNA on human laryngocarcinoma epithelial (Hep-2) cells. Compared with the traditional commercial vector Lipofectamine2000 (Lipo), CSSA exhibited lower cytotoxicity, more efficiently cellular uptake. Incubating with CSSA/siRNA, the survival rates of Hep-2 cells were significantly decreased comparing with either the group before transfection or Lipo/siRNA. CSSA is a promising carrier for efficient siRNA delivery and radiosensitization of laryngocarcinoma.
葡萄糖转运蛋白1（GLUT-1）被认为是恶性肿瘤缺氧的一种可能的内在标志物，这是喉癌放射抗性的一个重要因素。我们推测抑制GLUT-1表达可能会提高喉癌的放射敏感性。设计GLUT-1 siRNA以抑制GLUT-1表达，但高分子量和药物递送困难限制了其应用。在此，我们构建了一种糖脂聚合物壳寡糖接枝硬脂酸（CSSA），通过静电相互作用与siRNA偶联。研究了CSSA和CSSA/siRNA的特性，以及siRNA对人喉癌上皮（Hep-2）细胞的放射增敏作用。与传统商业载体Lipofectamine2000（Lipo）相比，CSSA表现出更低的细胞毒性、更高效的细胞摄取。与CSSA/siRNA孵育后，Hep-2细胞的存活率与转染前组或Lipo/siRNA组相比均显著降低。CSSA是一种用于高效递送siRNA和喉癌放射增敏的有前景的载体。
