Self-assembling peptide-based nanoparticles enhance anticancer effect of ellipticine in vitro and in vivo

Yan Wu,1,* Parisa Sadatmousavi,2,* Rong Wang,1 Sheng Lu,2 Yong-fang Yuan,1 P. Chen21Department of Pharmacy, No. 3 People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China; 2Department of Chemical Engineering, Unive...

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Autores principales: Wu Y, Sadatmousavi P, Wang R, Lu S, Yuan YF, Chen P
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2012
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Acceso en línea:https://doaj.org/article/04f5861af23c4052aa7c2d04f25b8993
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Sumario:Yan Wu,1,* Parisa Sadatmousavi,2,* Rong Wang,1 Sheng Lu,2 Yong-fang Yuan,1 P. Chen21Department of Pharmacy, No. 3 People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China; 2Department of Chemical Engineering, University of Waterloo, Waterloo, Ontario, Canada *Both authors contributed equally to this work.Background and methods: 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.Results: 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.Conclusion: 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.Keywords: self-assembling peptide, EAK16-II, ellipticine, nanoparticles, drug delivery, antitumor