Macromolecular delivery of 5-aminolaevulinic acid for photodynamic therapy using dendrimer conjugates
| Autor: | Christine Edwards, Adriana Casas, Alexander J. MacRobert, Alcira Batlle, Sophie O’Neill, Sherina Balaratnam, Sinan Battah, Paul S. Dobbin |
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| Rok vydání: | 2007 |
| Předmět: |
Keratinocytes
Dendrimers Cancer Research Skin Neoplasms Cell Survival Macromolecular Substances medicine.medical_treatment Protoporphyrins Photodynamic therapy Mice Structure-Activity Relationship chemistry.chemical_compound Dendrimer medicine Animals Humans Photosensitizer Cells Cultured Photosensitizing Agents Molecular Structure Protoporphyrin IX Chemistry Aminolevulinic Acid Porphyrin Microscopy Fluorescence Photochemotherapy Oncology Biochemistry Epidermoid carcinoma Drug delivery Carcinoma Squamous Cell Biophysics Phototoxicity |
| Zdroj: | Molecular Cancer Therapeutics. 6:876-885 |
| ISSN: | 1538-8514 1535-7163 |
| DOI: | 10.1158/1535-7163.mct-06-0359 |
| Popis: | Intracellular porphyrin generation following administration of 5-aminolaevulinic acid (5-ALA) has been widely used in photodynamic therapy. However, cellular uptake of 5-ALA is limited by its hydrophilicity, and improved means of delivery are therefore being sought. Highly branched polymeric drug carriers known as dendrimers present a promising new approach to drug delivery because they have a well-defined structure capable of incorporating a high drug payload. In this work, a dendrimer conjugate was investigated, which incorporated 18 aminolaevulinic acid residues attached via ester linkages to a multipodent aromatic core. The ability of the dendrimer to deliver and release 5-ALA intracellularly for metabolism to the photosensitizer, protoporphyrin IX, was studied in the transformed PAM 212 murine keratinocyte and A431 human epidermoid carcinoma cell lines. Up to an optimum concentration of 0.1 mmol/L, the dendrimer was significantly more efficient compared with 5-ALA for porphyrin synthesis. The intracellular porphyrin fluorescence levels showed good correlation with cellular phototoxicity following light exposure, together with minimal dark toxicity. Cellular uptake of the dendrimer occurs through endocytic routes predominantly via a macropinocytosis pathway. In conclusion, macromolecular dendritic derivatives are capable of delivering 5-ALA efficiently to cells for sustained porphyrin synthesis. [Mol Cancer Ther 2007;6(3):876–85] |
| Databáze: | OpenAIRE |
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