Magnetic nanoparticles enhance the anticancer activity of cathelicidin LL-37 peptide against colon cancer cells

Abstract

The pleiotropic activity of human cathelicidin LL-37 peptide includes an ability to suppress development of colon cancer cells. We hypothesized that the anticancer activity of LL-37 would improve when attached to the surface of magnetic nanoparticles (MNPs). Using colon cancer culture (DLD-1 cells and HT-29 cells), we evaluated the effects of MNPs, LL-37 peptide, its synthetic analog ceragenin CSA-13, and two novel nanosystems, ie, MNP@LL-37 and MNP@CSA-13, on cancer cell viability and apoptosis. Treatment of cancer cells with the LL-37 peptide linked to MNPs (MNP@LL-37) caused a greater decrease in cell viability and a higher rate of apoptosis compared with treatment using free LL-37 peptide. Additionally, we observed a strong ability of ceragenin CSA-13 and MNP@CSA-13 to induce apoptosis of DLD-1 cells. We found that both nanosystems were successfully internalized by HT-29 cells, and cathelicidin LL-37 and ceragenin CSA-13 might play a key role as novel homing molecules. These results indicate that the previously described anticancer activity of LL-37 peptide against colon cancer cells might be significantly improved using a theranostic approach.

Keywords:

• anticancer activity
• colorectal cancer
• ceragenin
• cathelicidin LL-37
• magnetic nanoparticles

Acknowledgments

This work was supported by grants from the National Science Centre, Poland (UMO-2012/07/B/NZ6/03504 to RB and UMO-2012/05/N/NZ7/00534 to KN) and the Medical University of Bialystok (144-27928P). IP also acknowledges “Studies, Research, Commercialization – A Support Programme for UMB Doctoral Students” Sub-measure 8.2.1 Human Capital Operational Programme, cofinanced by the European Union under the European Social Fund. The equipment used for analysis of data at the Center of Synthesis and Analysis BioNanoTechno, University of Bialystok, was funded by the European Union, as part of the Operational Program Development of Eastern Poland 2007–2013 (project POPW.01.03.00-20-034/09-00). The authors are grateful to Dariusz Pawlak and Arkadiusz Suraz˙yński for their help in conducting this research.

Disclosure

The authors report no conflicts of interest in this work.