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

Abstract

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

Acknowledgments

YW and PS contributed equally to this work. This project was supported by grant 10410711300 from the Shanghai Committee of Science and Technology, China. This research was financially supported by the Natural Sciences and Engineering Research Council of Canada, Canadian Foundation for Innovation, and the Canada Research Chairs Program for one of the coauthors (PC) and the Alexander Graham Bell Canada Graduate Scholarships for another coauthor (PS). The authors thank Dr Spafford for use of the fluorescence microscopy for uptake experiments, and Tewodros Mamo for assistance with fluorescence imaging at the University of Waterloo, Canada.

Disclosure

The authors report no conflicts of interest in this work.