Loading of fluorescent anticancer drug coralyne into micelles, liposomes and peptide self-assemblies

Low-toxic coralyne, a cationic benzo[c]phenanthridine type alkaloid, has received extensive attention because of its DNA- and RNA-targeting properties, and antimicrobial, anticancer activity, which is more pronounced compared to other protoberberine alkaloids [1-3]. In a previous work, we showed that the fluorescence intensity alteration of coralyne-impregnated silica gel plates allows the sensitive quantitative detection of a wide number of analytes by high-performance thin layer chromatographic techniques [4].

Due to its large flat aromatic structure, coralyne has a high tendency to penetrate into organized assemblies in solution, and we present here a fluorescence study of coralyne in different nano-heterogeneous media such as such as micelles, liposomes and peptide self-assemblies. A fluorescence emission increase is observed when coralyne probe is incorporated into these self-assemblies, as apolar microenvironments prevent non-radiative desexcitation pathways. The photochemical damage caused to the coralline is lower in the presence of these structures. Incorporation is confirmed by confocal fluorescence microscopy and Z-potential measurements. Furthermore, fluorescence measurements in the presence of the iodide ion quencher in the solution indicate that coralyne is protected into these structures. Coralyne uptake is more efficient in liposomes than in micelles, with partition coefficients more than an order of magnitude higher. Interestingly, results indicate that coralyne even incorporates into positively charged micellar aggregates, despite electrostatic repulsion, suggesting that the molecule penetrates deep into the self-assembly [5].

References

[1] W.D. Wilson, A.N. Gough, J.J. Doyle, M.W. Davidson, J. Med. Chem., 1976, 19, 1261–1263.

[2] S. Pal, S. Das, G.S. Kumar, M. Maiti, Curr. Sci., 1998, 75, 496–500.

[3] L.K. Wang, B.D. Roger, S.M. Hecht, Chem. Res. Toxicol., 1996, 9, 75–83.

[4] E. Mateos, V.L. Cebolla, L. Membrado, J. Vela, E.M. Gálvez, M. Matt and F.P. Cossio, J. Chromatogr. A, 2007, 1146, 251–257.

[5] R. Garriga et al., submitted.

Acknowledgements

Aragón Government (Grupo de Nanosensores y Sistemas Bioanalíticos (N&SB), ref. E25_23R).