Shanghai Key Laboratory of Cell Signaling and Diseases, School of Life Science and Technology, Tongji University, Shanghai 200092, PR China.
Int J Pharm. 2010 Mar 30;388(1-2):223-30. doi: 10.1016/j.ijpharm.2009.12.044. Epub 2010 Jan 5.
In this research, we intercalated anti-tumor drug podophyllotoxin (PPT) into layered double hydroxides (LDHs) and investigated the in vitro cytotoxicity to tumor cells, the cellular uptake and in vivo anti-tumor inhibition of PPT-LDH. The nanohybrids were prepared by a two-step method with the size of 80-90nm and the zeta potential of 20.3mV. The in vitro cytotoxicity experiment indicated that PPT-LDH nanoparticles show better anti-tumor efficacy than PPT and are more readily taken up by Hela cells. PPT-LDH shows a long-term suppression effect on the tumor growth, and enhances the apoptotic process of tumor cells. The in vivo tests reveal that delivery of PPT via LDH nanoparticles is more efficient, but the mice toxicity of PPT in PPT-LDH hybrids is reduced in comparison with PPT alone. Pharmacokinetics study displays a prolonged circulation time and an increased bioavailability of PPT-LDH than PPT. These observations imply that LDH nanoparticles are the potential carrier of anti-tumor drugs in a range of new therapeutic applications.
在这项研究中，我们将抗肿瘤药物鬼臼毒素（PPT）插入层状双氢氧化物（LDHs）中，并研究了其对肿瘤细胞的体外细胞毒性、细胞摄取以及 PPT-LDH 的体内抗肿瘤抑制作用。纳米杂化物通过两步法制备，粒径为 80-90nm，zeta 电位为 20.3mV。体外细胞毒性实验表明，PPT-LDH 纳米颗粒比 PPT 具有更好的抗肿瘤功效，并且更容易被 Hela 细胞摄取。PPT-LDH 对肿瘤生长具有长期抑制作用，并增强肿瘤细胞的凋亡过程。体内实验表明，通过 LDH 纳米颗粒输送 PPT 更有效，但与单独使用 PPT 相比，PPT-LDH 杂化物中 PPT 的小鼠毒性降低。药代动力学研究显示，PPT-LDH 的循环时间延长，生物利用度增加，优于 PPT。这些观察结果表明，LDH 纳米颗粒是一系列新治疗应用中抗肿瘤药物的潜在载体。
