Tian Baishun, Zhang Xiujuan, Yu Caitong, Zhou Mengjiao, Zhang Xiaohong
Functional Nano & Soft Materials Laboratory (FUNSOM) and Collaborative Innovation Center of Suzhou Nano Science and Technology Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, Jiangsu 215123, China.
Nanoscale. 2015 Feb 28;7(8):3588-93. doi: 10.1039/c4nr06743f.
In this paper, we investigated the aspect ratio (AR) effect of anticancer drug nanocrystals (NCs) on their cellular internalization efficiency, uptake mechanisms, biodistributions as well as in vitro and in vivo antitumor efficiencies. Both confocal imaging and flow cytometry show that shorter NCs with AR = 1.3 have a much faster cellular uptake rate and a much higher anticancer efficacy than longer NCs. All NCs with different ARs were found to enter the cells via an energy-dependent clathrin-mediated pathway. In vivo experiments indicate that NCs with higher ARs have a shorter half-life and are more easily captured by the liver, while the corresponding tumor uptake decreased. We also observed that NCs with the smallest AR have the highest therapeutic efficacy with appreciably less weight loss. These results would assist in the future design of drug NCs and may lead to the development of new drug nanostructures for biomedical applications.
在本文中，我们研究了抗癌药物纳米晶体（NCs）的长宽比（AR）对其细胞内化效率、摄取机制、生物分布以及体外和体内抗肿瘤效率的影响。共聚焦成像和流式细胞术均表明，长宽比为1.3的较短纳米晶体比较长纳米晶体具有更快的细胞摄取速率和更高的抗癌功效。发现所有具有不同长宽比的纳米晶体均通过能量依赖性网格蛋白介导的途径进入细胞。体内实验表明，长宽比更高的纳米晶体半衰期更短，更容易被肝脏捕获，而相应的肿瘤摄取则降低。我们还观察到，长宽比最小的纳米晶体具有最高的治疗效果，且体重减轻明显较少。这些结果将有助于未来药物纳米晶体的设计，并可能导致开发用于生物医学应用的新型药物纳米结构。
