New Derivatives of 5-Aminolevulinic Acid for Photodynamic Therapy: Chemical Synthesis and Porphyrin Production in In Vitro and In Vivo Biological Systems

Author(s):  
Aslak Godal ◽  
Nils O. Nilsen ◽  
Jo Klaveness ◽  
Jon Erik Branden ◽  
Jahn M. Nesland ◽  
...  
2019 ◽  
Vol 8 (2) ◽  
pp. 31-46
Author(s):  
D. A. Tzerkovsky ◽  
E. L. Protopovich ◽  
D. S. Stupak

In the present publication, authors have analyzed the results of using sonodynamic and sono-photodynamic therapy with photosensitizing agents of various classes (hematoporphyrin, 5-aminolevulinic acid, chlorin derivatives, etc.) in experimental oncology. In a number of in vitro and in vivo studies, the high antitumor efficacy of the above treatment methods has been proven. Ultrasonic treatment with a pulse frequency of 1–3 MHz and an intensity of 0.7 to 5 W/cm2 , independently and in combination with photo-irradiation of experimental tumors, can significantly improve the cytotoxic properties of photosensitizers. This became the basisfor testing the methodsin patients with malignant neoplasms of various localizations. Scientists fromSouth-East Asia presented the preliminary results of the use of sonodynamic and sono-photodynamic therapy with photosensitizers in the treatment of malignant pathology of the mammary gland, stomach, esophagus, prostate, lung and brain. Analysis of the obtained data indicates the absence of serious adverse events and an increase in the antitumor efficacy of treatment, which included these treatment methods with chlorin-type photosensitizers. 


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.


2000 ◽  
Vol 65 (3) ◽  
pp. 359-366 ◽  
Author(s):  
Fernanda Scarmato De Rosa ◽  
Juliana Maldonado Marchetti ◽  
José Antônio Thomazini ◽  
Antônio Cláudio Tedesco ◽  
Maria Vitória Lopes Badra Bentley

2005 ◽  
Vol 133 (2) ◽  
pp. P145-P146
Author(s):  
P CHUNG ◽  
J KIM ◽  
S LEE ◽  
C OH ◽  
J JUNG ◽  
...  

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3891 ◽  
Author(s):  
Tomohiro Osaki ◽  
Kiwamu Takahashi ◽  
Masahiro Ishizuka ◽  
Tohru Tanaka ◽  
Yoshiharu Okamoto

Artemisinin and its derivatives, including artesunate (ART) and artemether (ARM), exert anticancer effects in the micromolar range in drug and radiation-resistant cell lines. Artemisinin has been reported to sensitize cervical cancer cells to radiotherapy. In the present study, we determined whether ART and ARM could enhance the cytotoxicity of 5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT) against the mammary tumor cells of mice. The corrected PpIX fluorescence intensities in the control, 5-ALA, 5-ALA + ART, and 5-ALA + ARM groups were 3.385 ± 3.730, 165.7 ± 33.45, 139.0 ± 52.77, and 165.4 ± 51.10 a.u., respectively. At light doses of 3 and 5 J/cm2, the viability of 5-ALA-PDT-treated cells significantly decreased with ART (p < 0.01 and p < 0.01) and ARM treatment (p < 0.01 and p < 0.01). Besides, the number of annexin V-FITC and ethidium homodimer III-positive cells was greater in the 5-ALA-PDT with ARM group than that in the other groups. N-acetylcysteine could not significantly inhibit the percentages of apoptotic cells or inviable cells induced by 5-ALA-PDT with ARM. These reactive oxygen species-independent mechanisms might enhance cytotoxicity in 5-ALA-PDT with ARM-treated tumor cells, suggesting that the use of 5-ALA-PDT with ARM could be a new strategy to enhance PDT cytotoxicity against tumor cells. However, as these results are only based on in vitro studies, further in vivo investigations are required.


Author(s):  
Beata Osiecka ◽  
Kamil Jurczyszyn ◽  
Krzysztof Symonowicz ◽  
Andrzej Bronowicz ◽  
Paweł Ostasiewicz ◽  
...  

AbstractPhotodynamic therapy (PDT) is a well-known method for the treatment of malignant tumors, and its principles have been well established over the past 30 years. This therapy involves the application of a chemical called a photosensitizer and its subsequent excitation with light at the appropriate wavelength and energy. Topical photodynamic therapy with aminolevulinic acid (5-ALA) is an alternative therapy for many malignant processes, including nonmelanoma skin cancers such as basal-cell carcinoma (BCC). Our novel approach for this study was to use a liposomal formulation of 5-ALA and its methyl ester (commercially available as metvix) both in vitro and in vivo, and to check whether the liposome-entrapped precursors of photosensitizers can induce the expression of metalloproteinases (MMPs) in animal tumor cells and in other tissues from tumor-bearing rats and in selected cell lines in vitro. We also checked whether the application of tissue inhibitors of matrix metalloproteinases (TIMPs) has any effect on MMPs in the above-mentioned experimental models, and if they can cause complete inhibition of MMP expression. Immunohistochemical studies revealed that after the PDT, the intensity of expression of MMPs in healthy animals was very low and seen in single cells only. After the PDT in tumor-bearing rats, MMP-3 was expressed in the tumor cells with the highest intensity of staining in the tissues directly adjacent to the tumors, while MMP-2 and -9 were not found. In the control groups, there was no observed expression of MMPs. In vitro studies showed that MMP-3 was expressed in MCF-7 cells after PDT, but MMP-9 was not observed and MMP-2 was only seen in single cases. Our studies confirmed that the application of an MMP-3 inhibitor may block an induction of MMP-3 expression which had previously been initiated by PDT. The preliminary data obtained from cancer patients revealed that new precursors are effective in terms of PDT, and that using MMP inhibitors should be considered as a potential enhancing factor in clinical PDT.


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