Self-Assembling Peptide as a Potential Carrier for Hydrophobic Anticancer Drug Ellipticine: Complexation, Release and In Vitro Delivery
Self-Assembling Peptide as a Potential Carrier for Hydrophobic Anticancer Drug Ellipticine: Complexation, Release and In Vitro Delivery
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DOI：
10.1002/adfm.200800860
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发表时间：
2009-01-09
影响因子：
19
通讯作者：
Chen, P.
中科院分区：
文献类型：
--
作者：
Fung, Shan Yu;Yang, Hong;Chen, P.
自组装肽EAK 16-II能够稳定疏水化合物以在水溶液中形成微晶悬浮液。在这里，这种肽的能力，以稳定的疏水性抗癌剂椭圆树碱进行了研究。随时间监测肽-椭圆藤碱悬浮液的形成直至达到平衡。发现平衡时间取决于肽浓度。当肽浓度接近其临界聚集浓度时，平衡时间最短，为5 h。在EAK 16-II和椭圆树碱浓度的不同组合下，可以稳定椭圆树碱的两种分子状态（质子化或非质子化）。这些不同状态的椭圆树碱显著影响椭圆树碱从肽-椭圆树碱复合物释放到用于模拟细胞膜的卵磷脂酰胆碱囊泡中的释放动力学。质子化的椭圆藤碱从复合物到囊泡的转移速率比结晶椭圆藤碱快得多。这一观察结果也可能与所得复合物的尺寸有关，如从扫描电子显微镜照片中所揭示的。此外，质子化椭圆藤碱的配合物被发现对两种癌细胞系A549和MCF-7具有更好的抗癌活性。这项工作形成的肽-椭圆藤碱悬浮液在体外和体内的研究的基础上，导致未来的发展自组装肽为基础的疏水性抗癌药物的交付。
The self assembling peptide EAK16-II is capable of stabilizing hydrophobic compounds to form microcrystal suspensions in aqueous solution. Here, the ability of this peptide to stabilize the hydrophobic anticancer agent ellipticine is investigated. The formation of peptide-ellipticine suspensions is monitored with time until equilibrium is reached. The equilibration time is found to be dependent on the peptide concentration. When the peptide concentration is close to its critical aggregation concentration, the equilibration time is minimal at 5 h. With different combinations of EAK16-II and ellipticine concentrations, two molecular states (protonated or cyrstalline) of ellipticine could be stabilized. These different states of ellipticine significantly affect the release kinetics of ellipticine from the peptide-ellipticine complex into the egg phosphatidylcholine vesicles, which are used to mimic cell membranes. The transfer rate of protonated ellipticine from the complex to the vesicles is much faster than that of crystalline ellipticine. This observation may also be related to the size of the resulting complexes as revealed from the scanning electron micrographs. In addition, the complexes with protonated ellipticine are found to have a better anticancer activity against two cancer cell lines, A549 and MCF-7. This work forms the basis for studies of the peptide-ellipticine suspensions in vitro and in vivo leading to future development of self-assembling peptide-based delivery of hydrophobic anticancer drugs.