-
AAPS PharmSciTech Aug 2022Hypertrophic scar is a serious skin disorder, which reduces the patient's quality of life. 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy has been used to...
Hypertrophic scar is a serious skin disorder, which reduces the patient's quality of life. 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy has been used to treat patients with hypertrophic scar. However, the poor skin retention of 5-ALA limited the therapeutic effect. In this study, we constructed the 5-ALA-hyaluronic acid (HA) complex to potentially prolong the skin retention of 5-ALA for improving the therapeutic efficacy. HA is a polysaccharide with viscoelasticity and the carboxyl groups could conjugate with amino groups of 5-ALA via electrostatic interaction. The protoporphyrin IX (PpIX) assay revealed that 5-ALA-HA complexes markedly enhanced the skin retention, resulting in increased generation and accumulation of endogenous photosensitizer PpIX. Furthermore, 5-ALA-HA complexes allowed PpIX to be maintained at a high level for 12 h, much longer than the 3 h of 5-ALA alone. And then, the accumulative PpIX induced by 5-ALA-HA in human hypertrophic scar fibroblasts (HSF) was triggered by laser irradiation to produce sufficient reactive oxygen species, leading to efficient necrosis and apoptosis of HSF. In vivo therapeutic efficacy study indicated that 5-ALA-HA effectively reduced the appearance and scar thickness, and the scar elevation index with 5-ALA-HA treatment was significantly lower than other groups, suggesting that the 5-ALA-HA-treated scar became flattened and was closely matched to the unwounded tissues. Moreover, 5-ALA-HA treatment markedly downregulated the gene expression levels of α-SMA and TGF-β1, demonstrating attenuated the scar formation and growth. Therefore, the 5-ALA-HA complex enhancing skin retention and PpIX accumulation at the lesion site provide a promising therapeutic strategy for hypertrophic scar.
Topics: Aminolevulinic Acid; Cicatrix, Hypertrophic; Humans; Hyaluronic Acid; Photosensitizing Agents; Quality of Life
PubMed: 35927520
DOI: 10.1208/s12249-022-02370-1 -
Photodiagnosis and Photodynamic Therapy Dec 2023The treatment of deep-invasive cutaneous squamous cell carcinoma (cSCC) is difficult. Sonodynamic therapy (SDT) has showed advantages in large penetration depth, small...
BACKGROUND
The treatment of deep-invasive cutaneous squamous cell carcinoma (cSCC) is difficult. Sonodynamic therapy (SDT) has showed advantages in large penetration depth, small trauma, good repeatability, high targeting selectivity and effective protection for intact structure and function of tissues and organs.
OBJECTIVE
To study the efficacy and safety of 5-aminolevulinic acid SDT (ALA-SDT) in the treatment of cSCC.
METHODS
The absorption and transformation of ALA after co-incubation with cSCC were detected by UV-Vis and fluorescence absorption. The production of reactive oxygen species (ROS) when protoporphyrin IX (PpIX) excited with ultrasound was detected by ROS detection probe. Cytotoxicity of ALA-SDT to cSCC was detected with cytotoxicity indicators. The tumor volume changes and tumor weight of mice after ALA-SDT were detected. The effects of ALA-SDT on the growth of mice were evaluated through the changes in body weight of mice. Biosafety of treatment was further evaluated by histopathology to determine whether the tissues and organs of mice were affected after ALA-SDT.
RESULTS
ALA can be absorbed and converted into PpIX when incubated with cSCC cells and produces ROS with ultrasound irradiation. ALA-SDT showed a significant cytotoxicity on cSCC cells. With one session of ALA-SDT in vivo, tumor growth was slowed but not stopped and would proceed once treatment was ended. ALA-SDT had no significant effect on body weight changes and major tissues and organs of the mice.
CONCLUSION
ALA-SDT could safely and reduce cSCC cells growth both in vitro and in vivo.
Topics: Mice; Animals; Aminolevulinic Acid; Photosensitizing Agents; Ultrasonic Therapy; Carcinoma, Squamous Cell; Reactive Oxygen Species; Photochemotherapy; Skin Neoplasms; Body Weight; Cell Line, Tumor
PubMed: 37717674
DOI: 10.1016/j.pdpdt.2023.103801 -
The Laryngoscope Aug 2023Studies showed that photodynamic therapy (PDT) might be able to prevent vocal fold scar formation when treating laryngeal lesions. We aim to investigate if PDT improves...
OBJECTIVE
Studies showed that photodynamic therapy (PDT) might be able to prevent vocal fold scar formation when treating laryngeal lesions. We aim to investigate if PDT improves vocal wound healing and reduces scar formation in both prophylactic and remodeling procedures performed in vivo.
STUDY DESIGN
In vivo.
METHODS
Vocal fold stripping was performed in Sprague-Dawley rats. PDT was performed with intraperitoneal injection of 100 mg/kg 5-Aminolevulinic Acid (5-ALA) and 635 nm laser irradiation of 20, 40, and 60 J/cm . PDT was performed immediately after surgery to study the prophylactic effect and 4 weeks after surgery to study the remodeling effect. Gene expression was evaluated with real-time PCR at 1 week after PDT. Histologic evaluations were performed 12 weeks after PDT, including hematoxylin-eosin, Masson, Alcian blue staining, and immunohistochemical staining of collagen I and III.
RESULTS
PDT induced similar effects on the vocal fold wound healing outcomes in both prophylactic and remodeling procedures. Expression of MMP8, MMP13, HAS2, and TGFβ1 was significantly elevated. Histologic evaluation revealed significantly increased thickness, decreased density of collagen, and increased deposition of hyaluronic acid in the lamina propria. Immunohistochemistry also revealed better distribution and reduced density of collagen I and III. The most obvious changes were seen in the 60 J/cm PDT group.
CONCLUSION
PDT could significantly improve vocal wound healing by providing both prophylactic effects and remodeling effects. It may be a minimally invasive treatment for vocal fold lesions with slight vocal scarring, and may be used to treat acute or chronic vocal injury to reduce vocal scarring.
LEVEL OF EVIDENCE
N/A Laryngoscope, 133:1943-1951, 2023.
Topics: Rats; Animals; Cicatrix; Vocal Cords; Aminolevulinic Acid; Rats, Sprague-Dawley; Wound Healing; Collagen; Collagen Type I; Photochemotherapy
PubMed: 36278803
DOI: 10.1002/lary.30427 -
Journal of Photochemistry and... Aug 2019Photodynamic therapy (PDT) induced by protoporphyrin IX (PpIX) has been widely used in dermatological practices such as treatment of skin cancers. Clearance rate depends... (Review)
Review
Photodynamic therapy (PDT) induced by protoporphyrin IX (PpIX) has been widely used in dermatological practices such as treatment of skin cancers. Clearance rate depends on different factors such as light irradiation, skin oxygenation and drug penetration. The poor penetration of 5-aminolevulinic acid (5-ALA) with topical application is limited and restrains the production of PpIX which could restrict PDT outcomes. This review will focus on techniques already used to enhance drug penetration in human skin, and will present their results, advantages, and drawbacks. Chemical and physical pretreatments will be discussed. Chemical pre-treatments comprise of drug formulation modification, use of agents that modify the heme cycle, enhance PpIX formation, and the combination of differentiation-promoting agent prior to PDT. On the other hand, physical pretreatments affect the skin barrier by creating holes in the skin or by removing stratum corneum. To promote drug penetration, iontophoresis and temperature modulation are interesting alternative methods. Cellular mechanisms enrolled during chemical or physical pretreatments have been investigated in order to understand how 5-ALA penetrates the skin, why it is preferentially metabolized in PpIX in tumour cells, and how it could be accumulated in deeper skin layers. The objective of this review is to compare clinical trials that use innovative technology to conventional PDT treatment. Most of these pretreatments present good or even better clinical outcomes than usual PDT.
Topics: Aminolevulinic Acid; Drug Compounding; Humans; Liposomes; Micelles; Nanoparticles; Photochemotherapy; Photosensitizing Agents; Protoporphyrins; Skin Neoplasms
PubMed: 31295716
DOI: 10.1016/j.jphotobiol.2019.111544 -
Journal of Orthopaedic Surgery and... Mar 20205-Aminolevulinic acid (5-ALA), a fluorescent contrast agent, has been used for tumor paint and photodynamic therapy (PDT) for various tumors, but its use with soft...
BACKGROUND
5-Aminolevulinic acid (5-ALA), a fluorescent contrast agent, has been used for tumor paint and photodynamic therapy (PDT) for various tumors, but its use with soft tissue sarcomas is not well documented. Myxofibrosarcoma, a subtype of soft tissue sarcoma with a high local recurrence rate, may benefit from similar types of treatment. The purpose of this study was to analyze the effects of 5-ALA tumor paint and PDT on a myxofibrosarcoma cell line.
METHODS
Tumor paint was assessed by exposing micromass pellets of human adipose-derived stromal (ADS) cells or myxofibrosarcoma (MUG-Myx1) cells to 5-ALA. Cell pellets were then visualized using a microscope at established excitation and emission wavelengths. Corrected total cell fluorescence was calculated per accepted protocols. Photodynamic therapy was similarly assessed by exposing ADS and MUG-Myx1 cells to 5-ALA, with subsequent analysis via flow cytometry and real-time confocal microscopy.
RESULTS
The use of 5-ALA tumor paint led to a selective fluorescence in MUG-Myx1 cells. Findings were confirmed by flow cytometry. Interestingly, flow cytometry results showed progressive selective cell death with increasing 5-ALA exposure as a result of the PDT effect. PDT was further confirmed using confocal microscopy, which revealed progressive cellular bubble formation consistent with advancing stages of cell death-a finding that was not seen in control ADS cells.
CONCLUSIONS
5-ALA tumor paint and PDT were successfully used on a human myxofibrosarcoma cell line (MUG-Myx1). Results from this study showed both selective fluorescent tagging and selective cytotoxicity of 5-ALA toward malignant myxofibrosarcoma cells, while sparing benign adipose control cells. This finding was further confirmed in a dramatic time-lapse video, visually confirming active, targeted cell death. 5-ALA's two-pronged application of selective tumor identification and cytotoxicity may transform surgical and medical approaches for treating soft tissue sarcomas.
Topics: Aminolevulinic Acid; Cell Line, Tumor; Contrast Media; Fibroma; Fibrosarcoma; Humans; Microscopy, Confocal; Photochemotherapy
PubMed: 32138774
DOI: 10.1186/s13018-020-01606-9 -
Photodiagnosis and Photodynamic Therapy Jun 2024Actinic keratosis (AK) is a precancerous lesion that occurs in areas that are chronically exposed to sunlight and has the potential to develop into invasive cutaneous...
BACKGROUND
Actinic keratosis (AK) is a precancerous lesion that occurs in areas that are chronically exposed to sunlight and has the potential to develop into invasive cutaneous squamous cell carcinoma (cSCC). We investigated the efficacy of 20 % 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) with LED red light for the treatment of AK in Chinese patients by examining changes in dermoscopic features, histopathology and fluorescence after treatment.
METHODS
Twenty-eight patients with fourty-six AK lesions from March 2022 to September 2023 were treated with 20 % ALA, and 3 h later, they were irradiated with LED red light (80-100 mW/cm) for 20 min. A session of 20 % ALA-PDT was performed once a week for three consecutive weeks, and the dermoscopic, histopathological, fluorescent and photoaging outcomes were measured one week after the treatment.
RESULTS
One week after ALA-PDT, complete remission (CR) was reached in 53.6 % of patients. The CR of Grade I AK lesions was 100 %, that of Grade II lesions was 71.4 %, and that of Grade III lesions was 38.1 %. There was a significant improvement in the dermoscopic features, epidermal thickness and fluorescence of the AK lesions. The presence of red fluorescence decreased, and there was an association between CR and post-PDT fluorescence intensity. ALA-PDT also exhibited efficacy in treating photoaging, including fine lines, sallowness, mottled pigmentation, erythema, and telangiectasias, and improved the global score for photoaging. There were no serious adverse effects during or after ALA-PDT, and 82.1 % of the patients were satisfied with the treatment.
CONCLUSION
AK lesions can be safely and effectively treated with 20 % ALA-PDT with LED red light, which also alleviates photoaging in Chinese patients, including those with multiple AKs. This study highlights the possibility that fluorescence could be used to diagnose AK with peripheral field cancerization and evaluate the efficacy of ALA-PDT.
Topics: Keratosis, Actinic; Aminolevulinic Acid; Humans; Photochemotherapy; Photosensitizing Agents; Female; Male; Aged; Middle Aged; Dermoscopy; Aged, 80 and over; Fluorescence
PubMed: 38663488
DOI: 10.1016/j.pdpdt.2024.104100 -
Journal of the European Academy of... Feb 2017
Topics: Aminolevulinic Acid; Humans; Onychomycosis; Photochemotherapy; Photosensitizing Agents; Treatment Outcome
PubMed: 28128500
DOI: 10.1111/jdv.14100 -
Skinmed 2017
Topics: Administration, Topical; Aminolevulinic Acid; Female; Humans; Male; Photochemotherapy; Prognosis; Risk Assessment; Skin Neoplasms; Treatment Outcome
PubMed: 28528609
DOI: No ID Found -
BioFactors (Oxford, England) 2023Glioblastoma multiforme (GBM) is the most malignant type of cerebral neoplasm in adults with a poor prognosis. Currently, combination therapy with different anti-cancer...
Glioblastoma multiforme (GBM) is the most malignant type of cerebral neoplasm in adults with a poor prognosis. Currently, combination therapy with different anti-cancer agents is at the forefront of GBM research. Hence, this study aims to evaluate the potential anti-cancer synergy of a clinically approved neurokinin-1 receptor antagonist, aprepitant, and 5-aminolevulinic acid (5-ALA), a prodrug that elicits fluorescent porphyrins in gliomas on U-87 human GBM cells. We found that aprepitant and 5-ALA effectively inhibited GBM cell viability. The combinatorial treatment of these drugs exerted potent synergistic growth inhibitory effects on GBM cells. Moreover, aprepitant and 5-ALA induced apoptosis and altered the levels of apoptotic genes (up-regulation of Bax and P53 along with downregulation of Bcl-2). Furthermore, aprepitant and 5-ALA increased the accumulation of protoporphyrin IX, a highly pro-apoptotic and fluorescent photosensitizer. Aprepitant and 5-ALA significantly inhibited GBM cell migration and reduced matrix metalloproteinases (MMP-2 and MMP-9) activities. Importantly, all these effects were more prominent following aprepitant-5-ALA combination treatment than either drug alone. Collectively, the combination of aprepitant and 5-ALA leads to considerable synergistic anti-proliferative, pro-apoptotic, and anti-migratory effects on GBM cells and provides a firm basis for further evaluation of this combination as a novel therapeutic approach for GBM.
Topics: Adult; Humans; Aminolevulinic Acid; Glioblastoma; Aprepitant; Neurokinin-1 Receptor Antagonists; Cell Line, Tumor
PubMed: 37092793
DOI: 10.1002/biof.1953 -
Microbial Biotechnology Nov 2021Gamma-aminobutyric acid (GABA) and delta-aminolevulinic acid (ALA), playing important roles in agriculture, medicine and other fields, are multifunctional non-protein... (Review)
Review
Gamma-aminobutyric acid (GABA) and delta-aminolevulinic acid (ALA), playing important roles in agriculture, medicine and other fields, are multifunctional non-protein amino acids with similar and comparable properties and biosynthesis pathways. Recently, microbial synthesis has become an inevitable trend to produce GABA and ALA due to its green and sustainable characteristics. In addition, the development of metabolic engineering and synthetic biology has continuously accelerated and increased the GABA and ALA yield in microorganisms. Here, focusing on the current trends in metabolic engineering strategies for microbial synthesis of GABA and ALA, we analysed and compared the efficiency of various metabolic strategies in detail. Moreover, we provide the insights to meet challenges of realizing industrially competitive strains and highlight the future perspectives of GABA and ALA production.
Topics: Aminolevulinic Acid; Biosynthetic Pathways; Metabolic Engineering; Synthetic Biology; gamma-Aminobutyric Acid
PubMed: 33675575
DOI: 10.1111/1751-7915.13783