Derivatives of 5-Aminolevulinic Acid for Photodynamic Therapy

2007 ◽  
Vol 1 ◽  
pp. 1177391X0700100 ◽  
Author(s):  
Ryan F. Donnelly ◽  
Paul A. McCarron ◽  
David A. Woolfson

Photodynamic therapy (PDT) is a clinical treatment that combines the effects of visible light irradiation with subsequent biochemical events that arise from the presence of a photosensitising drug (possessing no dark toxicity) to cause destruction of selected cells. Today, the most common agent used in dermatological PDT is 5-aminolevulinic acid (ALA). As a result of its hydrophilic character, ALA penetrates skin lesions poorly when applied topically. Its systemic bioavailability is limited and it is known to cause significant side effects when given orally or intravenously. Numerous chemical derivatives of ALA have been synthesised with the aims of either improving topical penetration or enhancing systemic bioavailability, while reducing side effects. In vitro cell culture experiments with ALA derivatives have yielded promising results. However, if ALA derivatives are to demonstrate meaningful clinical benefits, a rational approach to topical formulation design is required, along with a systematic study aimed at uncovering the true potential of ALA derivatives in photodynamic therapy. With respect to systemic ALA delivery, more study is required in the developing area of ALA-containing dendrons and dendrimers.

2021 ◽  
Vol 14 (3) ◽  
pp. 229
Author(s):  
Yo Shinoda ◽  
Daitetsu Kato ◽  
Ryosuke Ando ◽  
Hikaru Endo ◽  
Tsutomu Takahashi ◽  
...  

5-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX). The photophysical feature of PpIX is clinically used in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). These clinical applications are potentially based on in vitro cell culture experiments. Thus, conducting a systematic review and meta-analysis of in vitro 5-ALA PDT experiments is meaningful and may provide opportunities to consider future perspectives in this field. We conducted a systematic literature search in PubMed to summarize the in vitro 5-ALA PDT experiments and calculated the effectiveness of 5-ALA PDT for several cancer cell types. In total, 412 articles were identified, and 77 were extracted based on our inclusion criteria. The calculated effectiveness of 5-ALA PDT was statistically analyzed, which revealed a tendency of cancer-classification-dependent sensitivity to 5-ALA PDT, and stomach cancer was significantly more sensitive to 5-ALA PDT compared with cancers of different origins. Based on our analysis, we suggest a standardized in vitro experimental protocol for 5-ALA PDT.


RSC Advances ◽  
2016 ◽  
Vol 6 (92) ◽  
pp. 89492-89498 ◽  
Author(s):  
Gabriel F. Gola ◽  
Gabriela M. Di Venosa ◽  
Daniel A. Sáenz ◽  
Gustavo H. Calvo ◽  
Gabriela M. Cabrera ◽  
...  

A chemically diverse set of 5-aminolevulinic acid prodrugs were obtained via a Passerini reaction and studied as photodinamic agents in vitro.


2015 ◽  
Vol 16 (12) ◽  
pp. 9936-9948 ◽  
Author(s):  
Mustafa El-Khatib ◽  
Carolin Tepe ◽  
Brigitte Senger ◽  
Maxine Dibué-Adjei ◽  
Markus Riemenschneider ◽  
...  

2002 ◽  
Vol 1 (5) ◽  
pp. 315-319 ◽  
Author(s):  
Christian S. Betz ◽  
Jin-Ping Lai ◽  
Wei Xiang ◽  
Philip Janda ◽  
Peter Heinrich ◽  
...  

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1760 ◽  
Author(s):  
Michy ◽  
Massias ◽  
Bernard ◽  
Vanwonterghem ◽  
Henry ◽  
...  

Advanced ovarian cancer is the most lethal gynecological cancer, with a high rate of chemoresistance and relapse. Photodynamic therapy offers new prospects for ovarian cancer treatment, but current photosensitizers lack tumor specificity, resulting in low efficacy and significant side-effects. In the present work, the clinically approved photosensitizer verteporfin was encapsulated within nanostructured lipid carriers (NLC) for targeted photodynamic therapy of ovarian cancer. Cellular uptake and phototoxicity of free verteporfin and NLC-verteporfin were studied in vitro in human ovarian cancer cell lines cultured in 2D and 3D-spheroids, and biodistribution and photodynamic therapy were evaluated in vivo in mice. Both molecules were internalized in ovarian cancer cells and strongly inhibited tumor cells viability when exposed to laser light only. In vivo biodistribution and pharmacokinetic studies evidenced a long circulation time of NLC associated with efficient tumor uptake. Administration of 2 mg.kg−1 free verteporfin induced severe phototoxic adverse effects leading to the death of 5 out of 8 mice. In contrast, laser light exposure of tumors after intravenous administration of NLC-verteporfin (8 mg.kg−1) significantly inhibited tumor growth without visible toxicity. NLC-verteporfin thus led to efficient verteporfin vectorization to the tumor site and protection from side-effects, providing promising therapeutic prospects for photodynamic therapy of cancer.


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