ALA and ALA hexyl ester in free and liposomal formulations for the photosensitisation of tumour organ cultures
Open accessAbstract
In spite of the wide range of tumours successfully treated with 5-aminolevulinic acid mediated photodynamic therapy, the fact that 5-aminolevulinic acid has low lipid solubility, limits its clinical application. More lipophilic 5-aminolevulinic acid prodrugs and the use of liposomal carriers are two approaches aimed at improving 5-aminolevulinic acid transmembrane access. In this study we used both 5-aminolevulinic acid and its hexyl ester in their free and encapsulated formulations to compare their corresponding endogenous synthesis of porphyrins. Employing murine tumour cultures, we found that neither the use of hexyl ester nor the entrapment of either 5-aminolevulinic acid or hexyl ester into liposomes increase the rate of tumour porphyrin synthesis. By light and electronic microscopy it was demonstrated that exposure of tumour explants to either free or liposomal 5-aminolevulinic acid and subsequent illumination induces the same type of subcellular damage. Mitochondria, endoplasmic reticulum and plasma membrane are the structures mostly injured in the early steps of photodynamic treatment. In a later stage, cytoplasmic and nuclear disintegration are observed. By electronic microscopy the involvement of the endocytic pathway in the incorporation of liposomal 5-aminolevulinic acid into the cells was shown.
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Administration of liposomes entrapping the ALA prodrug into tumor-bearing mice results in increment porphyrin biosynthesis as well as higher tumor to normal cells porphyrin ratio.
“Administration of liposomes entrapping the ALA prodrug into tumor-bearing mice results in increment porphyrin biosynthesis as well as higher tumor to normal cells porphyrin ratio [75].”
From Aminolevulinic Acid (ALA) as a Prodrug in Photodynamic Therapy of Cancer (2011) · cites this paper as [75]
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References 23 · Cited by 52
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- Authors
- Casas, A., Perotti, C., Saccoliti, M., Sacca, P., Fukuda, H., & del C Batlle, A. M.
- Affiliations
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- El Hospital General de Agudos Carlos G. Durand (AR)
- Venue
- British Journal of Cancer
- Published
- 2002-02-26
- Volume
- 86
- Issue
- 5
- Pages
- 837-842
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2375311
- OpenAlex
- W2053912922
- Cited by
- 52
- References
- 23
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 1 · 2021: 2 · 2020: 1 · 2018: 2 · 2016: 1 · 2015: 3 · 2014: 2 · 2013: 1 · 2012: 2
- FWCI
- 2.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Consejo Nacional de Investigaciones Científicas y Técnicas (00000)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Keywords
- 5-aminolevulinic acid, liposomal drug delivery, photodynamic therapy, porphyrin synthesis, photosensitization, mitochondrial damage, endoplasmic reticulum damage, cell membrane damage, endocytic uptake, prodrugs
- MeSH terms
- Aminolevulinic Acid, Animals, Liposomes, Male, Mice, Inbred BALB C, Microscopy, Electron, Mitochondria, Photochemotherapy, Porphyrins, Tumor Cells, Cultured, Photosensitizing Agents, Mice
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