Department of Pharmacy, No. 3 People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Int J Nanomedicine. 2012;7:3221-33. doi: 10.2147/IJN.S31858. Epub 2012 Jun 28.
Applications of the anticancer agent, ellipticine, have been limited by its hydrophobicity and toxicity. An efficient delivery system is required to exploit the enormous potential of this compound. Recently, EAK16-II, an ionic-complementary, self-assembling peptide, has been found to stabilize ellipticine in aqueous solution. Here, the anticancer activity of ellipticine encapsulated in EAK16-II (EAK-EPT) was evaluated in vitro and in vivo.
Our cellular uptake, toxicity, and apoptosis results in an A549 human lung carcinoma cell line indicate that EAK-EPT complexes are significantly more effective than treatment with EAK16-II or ellipticine alone. This is due to the ability of EAK16-II to stabilize ellipticine in a protonated state in well formed nanostructures approximately 200 nm in size. In vivo observations in an A549 nude mouse tumor model show higher antitumor activity and lower cytotoxicity of EAK-EPT complexes than in the control group treated with ellipticine alone. Tumor growth in animals was significantly inhibited after treatment with EAK-EPT complexes, and without any apparent side effects.
The anticancer activity observed in this study coupled with minimal side effects encourages further development of peptide-mediated delivery of anticancer drugs, ellipticine in the present case, for clinical application.
抗癌药物椭圆素的应用受到其疏水性和毒性的限制。需要一种有效的传递系统来挖掘这种化合物的巨大潜力。最近，已发现离子互补的自组装肽 EAK16-II 可稳定水中的椭圆素。本文评估了包封在 EAK16-II 中的椭圆素（EAK-EPT）的体外和体内抗癌活性。
我们在 A549 人肺癌细胞系中的细胞摄取、毒性和细胞凋亡研究表明，EAK-EPT 复合物比单独使用 EAK16-II 或椭圆素更有效。这是因为 EAK16-II 能够将椭圆素稳定在质子化状态下，形成约 200nm 大小的规整纳米结构。在 A549 裸鼠肿瘤模型中的体内观察表明，EAK-EPT 复合物的抗肿瘤活性更高，毒性更低，优于单独使用椭圆素的对照组。EAK-EPT 复合物处理后，动物的肿瘤生长明显受到抑制，且无明显副作用。
本研究观察到的抗癌活性以及最小的副作用鼓励进一步开发肽介导的抗癌药物（在本案例中为椭圆素）的临床应用。
