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Biochemical Society Transactions Apr 20225-Aminolevulinic acid-based photodynamic therapy (ALA-PDT) was first implemented over three decades ago and has since been mainly part of clinical practice for the... (Review)
Review
5-Aminolevulinic acid-based photodynamic therapy (ALA-PDT) was first implemented over three decades ago and has since been mainly part of clinical practice for the management of pre-cancerous and cancerous skin lesions. Photodynamic therapy relies on the combination of a photosensitizer, light and oxygen to cause photo-oxidative damage of cellular components. 5-Aminolevulinic acid (ALA) is a natural precursor of the heme biosynthetic pathway, which when exogenously administered leads to the accumulation of the photoactivatable protoporphyrin IX. Although, effective and providing excellent cosmetic outcomes, its use has been restricted by the burning, stinging, and prickling sensation associated with treatment, as well as cutaneous adverse reactions that may be induced. Despite intense research in the realm of drug delivery, pain moderation, and light delivery, a novel protocol design using sunlight has led to some of the best results in terms of treatment response and patient satisfaction. Daylight PDT is the protocol of choice for the management of treatment of multiple or confluent actinic keratoses (AK) skin lesions. This review aims to revisit the photophysical, physicochemical and biological characteristics of ALA-PDT, and the underlying mechanisms resulting in daylight PDT efficiency and limitations.
Topics: Aminolevulinic Acid; Humans; Keratosis, Actinic; Photochemotherapy; Sunlight; Treatment Outcome
PubMed: 35385082
DOI: 10.1042/BST20200822 -
Frontiers in Bioscience (Scholar... Dec 2023Mitochondrial dysfunction is considered an important mechanism in the pathogenesis of various diseases. Therefore, mitochondria are currently being considered as...
BACKGROUND
Mitochondrial dysfunction is considered an important mechanism in the pathogenesis of various diseases. Therefore, mitochondria are currently being considered as subjects for targeted therapies, particularly, phototherapy using 5-aminolevulinic acid. This study aimed to investigate the activity of mitochondria in cells with different mutation loads.
MATERIALS AND METHODS
The study was conducted using 11 cybrid lines obtained from the THP-1 cell line (a human monocytic leukemia cell line) and platelets of patients with different mitochondrial mutations.
RESULTS
Our results illustrate that 5-aminolevulinic acid was metabolized equally in all cell lines, however, there was a significant decrease in mitochondrial potential, which differed among lines.
CONCLUSIONS
The results of this study can be used to develop a personalized therapeutic approach based on different mitochondrial activities.
Topics: Humans; Aminolevulinic Acid; Photosensitizing Agents; Mitochondria; Cell Line; THP-1 Cells; Cell Line, Tumor
PubMed: 38163956
DOI: 10.31083/j.fbs1504017 -
Blood Nov 2023The acute hepatic porphyrias (AHPs) are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks precipitated by factors...
The acute hepatic porphyrias (AHPs) are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks precipitated by factors that upregulate hepatic 5-aminolevulinic acid synthase 1 (ALAS1) activity. Induction of hepatic ALAS1 leads to the accumulation of porphyrin precursors, in particular 5-aminolevulinic acid (ALA), which is thought to be the neurotoxic mediator leading to acute attack symptoms such as severe abdominal pain and autonomic dysfunction. Patients may also develop debilitating chronic symptoms and long-term medical complications, including kidney disease and an increased risk of hepatocellular carcinoma. Exogenous heme is the historical treatment for attacks and exerts its therapeutic effect by inhibiting hepatic ALAS1 activity. The pathophysiology of acute attacks provided the rationale to develop an RNA interference therapeutic that suppresses hepatic ALAS1 expression. Givosiran is a subcutaneously administered N-acetylgalactosamine-conjugated small interfering RNA against ALAS1 that is taken up nearly exclusively by hepatocytes via the asialoglycoprotein receptor. Clinical trials established that the continuous suppression of hepatic ALAS1 mRNA via monthly givosiran administration effectively reduced urinary ALA and porphobilinogen levels and acute attack rates and improved quality of life. Common side effects include injection site reactions and increases in liver enzymes and creatinine. Givosiran was approved by the US Food and Drug Administration and European Medicines Agency in 2019 and 2020, respectively, for the treatment of patients with AHP. Although givosiran has the potential to decrease the risk of chronic complications, long-term data on the safety and effects of sustained ALAS1 suppression in patients with AHP are lacking.
Topics: Humans; Aminolevulinic Acid; RNA Interference; Quality of Life; Porphyrias, Hepatic; Pain; Heme; Porphyrias
PubMed: 37027823
DOI: 10.1182/blood.2022018662 -
International Journal of Urology :... Feb 2017Photodynamic therapy using 5-aminolevulinic acid is a treatment method in which the fluorescent substance of protoporphyrin IX excessively accumulated specifically in... (Review)
Review
Photodynamic therapy using 5-aminolevulinic acid is a treatment method in which the fluorescent substance of protoporphyrin IX excessively accumulated specifically in cancer cells is excited by visible red or green light irradiation, and reactive oxygen is produced and injures cancer cells. Photodynamic therapy using 5-aminolevulinic acid less markedly influences the surrounding normal cells and tissue as a result of no accumulation of protoporphyrin IX, being a low-invasive, less harmful treatment localized to cancer. Furthermore, photodynamic therapy using 5-aminolevulinic acid is painless, requiring no anesthesia because localized lesions are treated at a low-energy level, and repeatedly applicable, unlike radiotherapy, and so is expected to be a new low-invasive treatment based on a concept completely different from existing treatments. In fact, photodynamic therapy using 5-aminolevulinic acid for bladder cancer was clinically demonstrated mainly for treatment-resistant bladder carcinoma in situ, and favorable outcomes have been obtained. Photodynamic therapy using 5-aminolevulinic acid are photodynamic technologies based on the common biological characteristic of cancers, and are expected as novel therapeutic strategies for many types of cancer.
Topics: Aminolevulinic Acid; Humans; Photochemotherapy; Photosensitizing Agents; Protoporphyrins; Treatment Outcome; Urinary Bladder; Urinary Bladder Neoplasms
PubMed: 28191719
DOI: 10.1111/iju.13291 -
Giornale Italiano Di Dermatologia E... Dec 2018Photodynamic therapy (PDT) is a well-established, non-invasive treatment for a variety of dermatologic disorders, including actinic keratosis. Furthermore, PDT results... (Review)
Review
Photodynamic therapy (PDT) is a well-established, non-invasive treatment for a variety of dermatologic disorders, including actinic keratosis. Furthermore, PDT results in marked improvements in the signs of skin aging, although currently there are no standardized guidelines for PDT in skin rejuvenation. Two types of PDT are available: conventional-PDT (c-PDT) and the newly introduced daylight-PDT (DL-PDT). Both require a topical photosensitizer, a light source and oxygen, and both are comparable regarding safety and efficacy for treatment of photo-induced skin aging. Treatment is particularly effective for improvement of fine wrinkles, skin roughness, actinic elastosis and mottled hyperpigmentation. The most widely studied topical sensitizers used in PDT are 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL). A range of pre-treatment procedures help improve skin absorption of the photosensitizer and lead to significantly improved efficacy. A variety of activating light sources can be used for c-PDT, while DL-PDT uses natural daylight, making it easier to treat larger areas of photodamaged skin. A major limitation of c-PDT is significant treatment-related pain, but DL-PDT has proved to be an almost pain-free procedure. Treatment duration is based on individual patient need but most patients receive 2 to 3 treatment cycles, with results fully evident 3-6 months post-treatment. PDT for aesthetic-cosmetic treatments has established its value in modern procedural dermatology as mono- or combination therapy. A major, unique advantage of PDT is that it is a non-invasive treatment that effectively rejuvenates photodamaged skin, while successfully treating a range of dermatologic conditions, including prevention and therapy of pre-cancerous actinic keratosis.
Topics: Aminolevulinic Acid; Humans; Keratosis, Actinic; Light; Pain; Photochemotherapy; Photosensitizing Agents; Rejuvenation; Skin Aging; Time Factors; Treatment Outcome
PubMed: 29600693
DOI: 10.23736/S0392-0488.18.05982-5 -
Acta Neurochirurgica Apr 2024Glioblastoma is the most common primary malignant brain tumor. Despite advances in multimodal concepts over the last decades, prognosis remains poor. Treatment of... (Review)
Review
Glioblastoma is the most common primary malignant brain tumor. Despite advances in multimodal concepts over the last decades, prognosis remains poor. Treatment of patients with glioblastoma remains a considerable challenge due to the infiltrative nature of the tumor, rapid growth rates, and tumor heterogeneity. Standard therapy consists of maximally safe microsurgical resection followed by adjuvant radio- and chemotherapy with temozolomide. In recent years, local therapies have been extensively investigated in experimental as well as translational levels. External stimuli-responsive therapies such as Photodynamic Therapy (PDT), Sonodynamic Therapy (SDT) and Radiodynamic Therapy (RDT) can induce cell death mechanisms via generation of reactive oxygen species (ROS) after administration of five-aminolevulinic acid (5-ALA), which induces the formation of sensitizing porphyrins within tumor tissue. Preliminary data from clinical trials are available. The aim of this review is to summarize the status of such therapeutic approaches as an adjunct to current standard therapy in glioblastoma.
Topics: Humans; Glioblastoma; Aminolevulinic Acid; Fluorescence; Temozolomide; Reactive Oxygen Species
PubMed: 38563988
DOI: 10.1007/s00701-024-06049-3 -
Biochemical Pharmacology Nov 20235-Aminolevulinic acid (ALA) has been approved by the U. S. FDA for fluorescence-guided resection of high-grade glioma and photodynamic therapy (PDT) of superficial skin... (Review)
Review
5-Aminolevulinic acid (ALA) has been approved by the U. S. FDA for fluorescence-guided resection of high-grade glioma and photodynamic therapy (PDT) of superficial skin precancerous and cancerous lesions. As a prodrug, ALA administered orally or topically is metabolized in the heme biosynthesis pathway to produce protoporphyrin IX (PpIX), the active drug with red fluorescence and photosensitizing property. Preferential accumulation of PpIX in tumors after ALA administration enables the use of ALA for PpIX-mediated tumor fluorescence diagnosis and PDT, functioning as a photo-theranostic agent. Extensive research is currently underway to further enhance ALA-mediated PpIX tumor disposition for better tumor visualization and treatment. Particularly, the discovery of PpIX as a specific substrate of ATP binding cassette subfamily G member 2 (ABCG2) opens the door to therapeutic enhancement with ABCG2 inhibitors. Studies with human tumor cell lines and human tumor samples have demonstrated ABCG2 as an important biological determinant of reduced ALA-PpIX tumor accumulation, inhibition of which greatly enhances ALA-PpIX fluorescence and PDT response. These studies strongly support targeting ABCG2 as an effective therapeutic enhancement approach. In this review, we would like to summarize current research of ABCG2 as a drug efflux transporter in multidrug resistance, highlight previous works on targeting ABCG2 for therapeutic enhancement of ALA, and provide future perspectives on how to translate this ABCG2-targeted therapeutic enhancement strategy from bench to bedside.
Topics: Humans; Aminolevulinic Acid; ATP Binding Cassette Transporter, Subfamily G, Member 2; Photochemotherapy; Protoporphyrins; Cell Line, Tumor; Photosensitizing Agents; Neoplasm Proteins
PubMed: 37858868
DOI: 10.1016/j.bcp.2023.115851 -
Applied Microbiology and Biotechnology Sep 20145-Aminolevulinic acid (ALA), an important intermediate in tetrapyrrole biosynthesis in organisms, has been widely applied in many fields, such as medicine, agriculture,... (Review)
Review
5-Aminolevulinic acid (ALA), an important intermediate in tetrapyrrole biosynthesis in organisms, has been widely applied in many fields, such as medicine, agriculture, and the food industry, due to its biochemical characteristics. Research efforts supporting the microbial production of ALA have received increasing interest due to its dominant advantages over chemical synthesis, including higher yields, lesser pollutant emissions, and a lesser monetary cost. ALA synthesis using photosynthetic bacteria (PSB) is a promising approach in various microbial synthesis methods. In this review, recent advances on the microbial production of ALA with an emphasis on PSB are summarized, the key enzymes in the biosynthesis pathway (especially the relationship between key enzymes and key genes) are detailed, regulation strategies are described, and the significant influencing factors on the ALA biosynthesis and application of ALA are outlined. Furthermore, the eco-friendly perspective involving the combination of wastewater treatment and microbial production of ALA is conceived.
Topics: Aminolevulinic Acid; Bacteria; Biotechnology; Gene Expression Regulation, Bacterial; Metabolic Networks and Pathways; Wastewater; Water Purification
PubMed: 25022665
DOI: 10.1007/s00253-014-5925-y -
ACS Nano Jul 2023Mitochondria-specific photosensitizer accumulation is highly recommended for photodynamic therapy and mitochondrial DNA (mtDNA) oxidative damage-based innate...
Mitochondria-specific photosensitizer accumulation is highly recommended for photodynamic therapy and mitochondrial DNA (mtDNA) oxidative damage-based innate immunotherapy but remains challenging. 5-Aminolevulinic acid (ALA), precursor of photosensitizer protoporphyrin IX (PpIX), can induce the exclusive biosynthesis of PpIX in mitochondria. Nevertheless, its photodynamic effect is limited by the intracellular biotransformation of ALA in tumors. Here, we report a photosensitizer metabolism-regulating strategy using ALA/DNAzyme-co-loaded nanoparticles (ALA&Dz@ZIF-PEG) for mitochondria-targeting photodynamic immunotherapy. The zeolitic imidazolate framework (ZIF-8) nanoparticles can be disassembled and release large amounts of zinc ions (Zn) within tumor cells. Notably, Zn can relieve tumor hypoxia for promoting the conversion of ALA to PpIX. Moreover, Zn acts as a cofactor of rationally designed DNAzyme for silencing excessive ferrochelatase (FECH; which catalyzes PpIX into photoinactive Heme), cooperatively promoting the exclusive accumulation of PpIX in mitochondria via the "open source and reduced expenditure" manner. Subsequently, the photodynamic effects derived from PpIX lead to the damage and release of mtDNA and activate the innate immune response. In addition, the released Zn further enhances the mtDNA/cGAS-STING pathway mediated innate immunity. The ALA&Dz@ZIF-PEG system induced 3 times more PpIX accumulation than ALA-loaded liposome, significantly enhancing tumor regression in xenograft tumor models.
Topics: Humans; Photosensitizing Agents; DNA, Catalytic; Cell Line, Tumor; Aminolevulinic Acid; Photochemotherapy; Mitochondria; DNA, Mitochondrial; Nanoparticles; Immunotherapy; Protoporphyrins
PubMed: 37438324
DOI: 10.1021/acsnano.3c03308 -
Plant Cell Reports Aug 20215-aminolevulinic acid (ALA) modulates various defense systems in plants and confers abiotic stress tolerance. Enhancement of crop production is a challenge due to... (Review)
Review
5-aminolevulinic acid (ALA) modulates various defense systems in plants and confers abiotic stress tolerance. Enhancement of crop production is a challenge due to numerous abiotic stresses such as, salinity, drought, temperature, heavy metals, and UV. Plants often face one or more abiotic stresses in their life cycle because of the challenging growing environment which results in reduction of growth and yield. Diverse studies have been conducted to discern suitable mitigation strategies to enhance crop production by minimizing abiotic stress. Exogenous application of different plant growth regulators is a well-renowned approach to ameliorate adverse effects of abiotic stresses on crop plants. Among the numerous plant growth regulators, 5-aminolevulinic acid (ALA) is a novel plant growth regulator, also well-known to alleviate the injurious effects of abiotic stresses in plants. ALA enhances abiotic stress tolerance as well as growth and yield by regulating photosynthetic and antioxidant machineries and nutrient uptake in plants. However, the regulatory roles of ALA in plants under different stresses have not been studied and assembled systematically. Also, ALA-mediated abiotic stress tolerance mechanisms have not been fully elucidated yet. Therefore, this review discusses the role of ALA in crop growth enhancement as well as its ameliorative role in abiotic stress mitigation and also discusses the ALA-mediated abiotic stress tolerance mechanisms and its limitation and future promises for sustainable crop production.
Topics: Aminolevulinic Acid; Crops, Agricultural; Droughts; Metals, Heavy; Plant Growth Regulators; Plant Physiological Phenomena; Salinity; Soil Pollutants; Stress, Physiological
PubMed: 33839877
DOI: 10.1007/s00299-021-02690-9