Photosensitization of skin fibroblasts and HeLa cells by three chlorin derivatives: Role of chemical structure and delivery vehicle.

Abstract

The chemical nature of the sensitizer and its selective uptake by malignant cells are decisive to choose an appropriate biocompatible carrier, able to preserve the photosensitizing characteristics of the dye. In this paper we demonstrate the photodynamic properties of three chlorins, derived from chlorophyll a, and the usefulness of liposomal carriers to design pharmaceutical formulations. The chlorins have been quantitatively incorporated into stable liposomes obtained from a mixture of L-alpha-palmitoyloleoylphosphatidylcholine and L-alpha-dioleoylphosphatidylserine in a 13.5:1.5 molar ratio (POPC/OOPS-liposomes). The chlorin uptake by skin fibroblasts increases steadily, reaching in all cases a plateau level dependent on both the chlorin structure and the vehicle employed. The photophysical properties of the three chlorins in THF are nearly identical and fulfill the requirements for a PDT photosensitizer. Incorporation of chlorins into liposomes induces important changes in their photophysics, but does not impair their cellular uptake or their cell photosensitization ability. In fact we observe in the cells the same photophysical behavior as in THF solution. Specifically, we demonstrate, by recording the near-IR phosphorescence of 1O2, that the chlorins are able to photosensitize the production of 1O2 in the cell membrane. The cell-photosensitization efficiency depended on the chlorin and cell line nature, the carrier, and the length of pre-incubation and post-irradiation periods. The high photodynamic activity of chlorin-loaded liposomes and the possibility to design liposomal carriers to achieve a specific target site favors this approach to obtain an eventual pharmaceutical formulation.

• Authors: Fernando Postigo, M Luisa Sagristá, M Africa De Madariaga, Santi Nonell, Margarita Mora
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1758 Issue 5 Pg. 583-96 (May 2006) ISSN: 0006-3002 [Print] Netherlands
• PMID: 16740249 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Liposomes
• Pharmaceutical Vehicles
• Photosensitizing Agents
• Porphyrins
• chlorin

Topics

• Fibroblasts (drug effects, radiation effects)
• HeLa Cells
• Humans
• Infrared Rays
• Liposomes
• Molecular Structure
• Pharmaceutical Vehicles
• Photochemotherapy
• Photosensitizing Agents (chemistry, pharmacology)
• Porphyrins (chemistry, pharmacology)
• Skin (cytology, drug effects, radiation effects)
• Spectrometry, Fluorescence