Li Lin, Yao Xuxiang, Wei Pengyao, He Dongdong, Ding Qiaojiao, Bai Bing, Lv Xiuyi, Kuzuya Akinori, Wang Yuling, Wu Kerong, Wang Kaizhe, Zheng Jianping
Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology, Ningbo Cixi Institute of Biomedical Engineering, Ningbo Institute of Materials Technology and Engineering of Chinese Academy of Sciences, Ningbo 315300, P. R. China.
The First Affiliated Hospital of Ningbo University, Ningbo University, Ningbo 315300, P. R. China.
ACS Omega. 2024 Jul 29;9(31):33765-33772. doi: 10.1021/acsomega.4c03091. eCollection 2024 Aug 6.
Sunitinib (SUN) is a first-line drug for the treatment of renal clear carcinoma cells by targeting receptor tyrosine kinases (RTK) on the cell membrane. However, the effective delivery of SUN to the cell membrane remains a significant challenge. In this study, we fabricated precisely structured DNA nanotapes with strong surface SUN adhesion, enabling RTK inhibition of renal clear carcinoma cells. In our design, the precisely assembled linear topological six-helical-bundle DNA origami serves as the framework, and positively charged chitosan is adsorbed onto the DNA origami surface, thereby forming DNA nanotapes. The SUN was efficiently loaded onto the surface of the DNA nanotapes by electrostatic interaction. We found that DNA nanotapes exhibit excellent stability in serum. Importantly, DNA nanotapes carrying SUN can achieve prolonged cell membrane retention and inhibit RTK, thereby enhancing cytotoxicity toward 786-0 cells. Taken together, this study provides a promising candidate platform for the efficient delivery of cell membrane receptor inhibitors in anticancer therapy.
舒尼替尼(SUN)是一种通过靶向细胞膜上的受体酪氨酸激酶(RTK)来治疗肾透明癌细胞的一线药物。然而,将SUN有效递送至细胞膜仍然是一项重大挑战。在本研究中,我们制备了具有强表面SUN粘附性的精确结构DNA纳米带,能够抑制肾透明癌细胞的RTK。在我们的设计中,精确组装的线性拓扑六螺旋束DNA折纸作为框架,带正电荷的壳聚糖吸附在DNA折纸表面,从而形成DNA纳米带。SUN通过静电相互作用被有效地负载到DNA纳米带表面。我们发现DNA纳米带在血清中表现出优异的稳定性。重要的是,携带SUN的DNA纳米带能够实现细胞膜的长时间保留并抑制RTK,从而增强对786-0细胞的细胞毒性。综上所述,本研究为抗癌治疗中细胞膜受体抑制剂的高效递送提供了一个有前景的候选平台。