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Scientific Reports Jun 2023Boron neutron capture therapy (BNCT) is a high-LET particle radiotherapy clinically tested for treating malignant gliomas. Boronophenylalanine (BPA), a boron-containing...
Boron neutron capture therapy (BNCT) is a high-LET particle radiotherapy clinically tested for treating malignant gliomas. Boronophenylalanine (BPA), a boron-containing phenylalanine derivative, is selectively transported into tumor cells by amino acid transporters, making it an ideal agent for BNCT. In this study, we investigated whether the amino acid 5-aminolevulinic acid (ALA) could sensitize glioma stem cells (GSCs) to BNCT by enhancing the uptake of BPA. Using human and mouse GSC lines, pre-incubation with ALA increased the intracellular accumulation of BPA dose-dependent. We also conducted in vivo experiments by intracerebrally implanting HGG13 cells in mice and administering ALA orally 24 h before BPA administration (ALA + BPA-BNCT). The ALA preloading group increased the tumor boron concentration and improved the tumor/blood boron concentration ratio, resulting in improved survival compared to the BPA-BNCT group. Furthermore, we found that the expression of amino acid transporters was upregulated following ALA treatment both in vitro and in vivo, particularly for ATB. This suggests that ALA may sensitize GSCs to BNCT by upregulating the expression of amino acid transporters, thereby enhancing the uptake of BPA and improving the effectiveness of BNCT. These findings have important implications for strategies to improve the sensitivity of malignant gliomas to BPA-BNCT.
Topics: Humans; Animals; Mice; Aminolevulinic Acid; Boron Neutron Capture Therapy; Boron; Glioma; Neoplastic Stem Cells; Boron Compounds; Brain Neoplasms
PubMed: 37349515
DOI: 10.1038/s41598-023-37296-6 -
Angewandte Chemie (International Ed. in... May 2023The efficacy of photodynamic therapy (PDT) depends on the subcellular localization of photosensitizers. Herein, we report a dual-organelle-targeted nanoparticle platform...
The efficacy of photodynamic therapy (PDT) depends on the subcellular localization of photosensitizers. Herein, we report a dual-organelle-targeted nanoparticle platform for enhanced PDT of cancer. By grafting 5-aminolevulinic acid (ALA) to a Hf -based nanoscale metal-organic layer (Hf-MOL) via carboxylate coordination, ALA/Hf-MOL enhanced ALA delivery and protoporphyrin IX (PpIX) synthesis in mitochondria, and trapped the Hf-MOL comprising 5,15-di-p-benzoatoporphyrin (DBP) photosensitizers in lysosomes. Light irradiation at 630 nm simultaneously excited PpIX and DBP to generate singlet oxygen and rapidly damage both mitochondria and lysosomes, leading to synergistic enhancement of the PDT efficacy. The dual-organelle-targeted ALA/Hf-MOL outperformed Hf-MOL in preclinical PDT studies, with a 2.7-fold lower half maximal inhibitory concentration in cytotoxicity assays in vitro and a 3-fold higher cure rate in a colon cancer model in vivo.
Topics: Aminolevulinic Acid; Photosensitizing Agents; Porphyrins; Photochemotherapy; Mitochondria; Metals; Cell Line, Tumor
PubMed: 36997341
DOI: 10.1002/anie.202301910 -
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 -
Photochemical & Photobiological... Oct 2020Oral lichen planus (OLP) is a chronic inflammatory and immune-mediated disease affecting the oral mucosa. OLP presents with asymptomatic, lacelike white stripes and/or... (Review)
Review
Oral lichen planus (OLP) is a chronic inflammatory and immune-mediated disease affecting the oral mucosa. OLP presents with asymptomatic, lacelike white stripes and/or symptomatic red, ulcerated mucous membranes. Eating, drinking and oral hygiene procedures may be painful resulting in reduced quality of life (QOL). The histopathological picture is a zone of cellular infiltrate, mainly CD8+ cells, in the superficial layer of the connective tissue and signs of liquefaction degeneration of the basal membrane. Conventional treatment is corticosteroids. Local and systemic side effects are common, and patients may develop drug resistance. The intention with this article is to demonstrate the heterogeneity in photodynamic therapy (PDT) of OLP. A search in PubMed, Embase (Ovid) and Medline (Ovid) identified seventeen clinical studies investigating PDT of OLP. Only five were randomised controlled studies and the study groups varied from 5 to 50 patients. Five different photosensitisers or precursors were tested. Both broadband spectrum lamps, lasers and light-emitting-diodes (LEDs), with wavelengths from 420 nm to 682 nm, were used. The number of treatment sessions varied from one to ten. The patients were followed up for 0 to 48 months, but in thirteen studies the post treatment observation time was ≤6 months. Single arm studies demonstrated improvement of OLP except in one study. In all controlled studies except for one, PDT was superior or equal to conventional treatment. The majority of patients experienced a slight burning sensation during light activation, but no serious adverse events were reported. Only few studies examined the effect of PDT on a cellular level.
Topics: Aminolevulinic Acid; Humans; Lichen Planus, Oral; Photochemotherapy; Photosensitizing Agents
PubMed: 32945823
DOI: 10.1039/d0pp00249f -
Combined therapy of 5-aminolevulinic acid photodynamic therapy and intense pulsed light for rosacea.Lasers in Medical Science Dec 2022Rosacea is difficult to treat. Therefore, new alternative modalities are necessary to demonstrate. The present study was conducted to assess the efficacy and safety of...
Rosacea is difficult to treat. Therefore, new alternative modalities are necessary to demonstrate. The present study was conducted to assess the efficacy and safety of the combined therapy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and intense pulsed light (IPL) for rosacea to provide a new treatment option for rosacea. The study was conducted from November 2017 to April 2019 at the Department of Dermatology, The First Hospital of China Medical University. Patients aged 18-65 years and diagnosed clinically as erythematotelangiectatic (ET) or papulopustular (PP) rosacea were enrolled. Three times of ALA-PDT at 10 days interval followed by 3 times of IPL at 3-4 weeks interval were defined as 1 session and applied to the whole face of each patient. ALA-PDT: 5% ALA, red light (fluency dose 60-100 mW/cm, 20 min); IPL: 560/590/640 nm, double/triple-pulse mode, pulse width 3.0 to 4.5 ms, delay time 30-40 ms, energy fluency 14-17 J/cm. Ten patients were enrolled in the study. Among them, 4 patients received only 1 session, while 6 patients received 2 sessions. After all treatments, 50% of patients achieved 75-100% improvement, and 30% achieved 50-75% improvement. Forty percent of patients were graded very satisfaction and 30% graded moderate satisfaction. All noninvasive measurements showed no significant differences among all time points (p > 0.05). The side effects were pain, burning sensation, itching, erythema, desquamation, slight edema, slight exudation, and hyperpigmentation. All of which were tolerable and recovered in a few days. The combined therapy of ALA-PDT and IPL showed an effective option for rosacea with a safety profile.
Topics: Humans; Aminolevulinic Acid; Photosensitizing Agents; Photochemotherapy; Rosacea; Erythema; Treatment Outcome; Intense Pulsed Light Therapy
PubMed: 36562857
DOI: 10.1007/s10103-022-03685-y -
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 -
The Journal of Biological Chemistry Mar 2022Heme is a critical biomolecule that is synthesized in vivo by several organisms such as plants, animals, and bacteria. Reflecting the importance of this molecule,... (Review)
Review
Heme is a critical biomolecule that is synthesized in vivo by several organisms such as plants, animals, and bacteria. Reflecting the importance of this molecule, defects in heme biosynthesis underlie several blood disorders in humans. Aminolevulinic acid synthase (ALAS) initiates heme biosynthesis in α-proteobacteria and nonplant eukaryotes. Debilitating and painful diseases such as X-linked sideroblastic anemia and X-linked protoporphyria can result from one of more than 91 genetic mutations in the human erythroid-specific enzyme ALAS2. This review will focus on recent structure-based insights into human ALAS2 function in health and how it dysfunctions in disease. We will also discuss how certain genetic mutations potentially result in disease-causing structural perturbations. Furthermore, we use thermodynamic and structural information to hypothesize how the mutations affect the human ALAS2 structure and categorize some of the unique human ALAS2 mutations that do not respond to typical treatments, that have paradoxical in vitro activity, or that are highly intolerable to changes. Finally, we will examine where future structure-based insights into the family of ALA synthases are needed to develop additional enzyme therapeutics.
Topics: 5-Aminolevulinate Synthetase; Aminolevulinic Acid; Anemia, Sideroblastic; Animals; Genetic Diseases, X-Linked; Heme; Humans; Structure-Activity Relationship
PubMed: 35093382
DOI: 10.1016/j.jbc.2022.101643 -
Journal of Nanobiotechnology Jul 2022Radiodynamic therapy (RDT) holds the potential to overcome the shallow tissue penetration issue associated with conventional photodynamic therapy (PDT). To this end,...
BACKGROUND
Radiodynamic therapy (RDT) holds the potential to overcome the shallow tissue penetration issue associated with conventional photodynamic therapy (PDT). To this end, complex and sometimes toxic scintillator-photosensitizer nanoconjugates are often used, posing barriers for large-scale manufacturing and regulatory approval.
METHODS
Herein, we report a streamlined RDT strategy based on CsI(Na)@MgO nanoparticles and 5-aminolevulinic acid (5-ALA). 5-ALA is a clinically approved photosensitizer, converted to protoporphyrin IX (PpIX) in cancer cells' mitochondria. CsI(Na)@MgO nanoparticles produce strong ~ 410 nm X-ray luminescence, which matches the Soret band of PpIX. We hypothesize that the CsI(Na)@MgO-and-5-ALA combination can mediate RDT wherein mitochondria-targeted PDT synergizes with DNA-targeted irradiation for efficient cancer cell killing. Because scintillator nanoparticles and photosensitizer are administered separately, the approach forgoes issues such as self-quenching or uncontrolled release of photosensitizers.
RESULTS
When tested in vitro with 4T1 cells, the CsI(Na)@MgO and 5-ALA combination elevated radiation-induced reactive oxygen species (ROS), enhancing damages to mitochondria, DNA, and lipids, eventually reducing cell proliferation and clonogenicity. When tested in vivo in 4T1 models, RDT with the CsI(Na)@MgO and 5-ALA combination significantly improved tumor suppression and animal survival relative to radiation therapy (RT) alone. After treatment, the scintillator nanoparticles, made of low-toxic alkali and halide elements, were efficiently excreted, causing no detectable harm to the hosts.
CONCLUSIONS
Our studies show that separately administering CsI(Na)@MgO nanoparticles and 5-ALA represents a safe and streamlined RDT approach with potential in clinical translation.
Topics: Aminolevulinic Acid; Animals; Cell Line, Tumor; Magnesium Oxide; Nanoparticles; Photochemotherapy; Photosensitizing Agents
PubMed: 35842630
DOI: 10.1186/s12951-022-01537-z -
International Journal of Molecular... May 2023Cancer is the leading cause of death worldwide and several anticancer therapies take advantage of the ability of reactive oxygen species to kill cancer cells. Added to... (Review)
Review
Cancer is the leading cause of death worldwide and several anticancer therapies take advantage of the ability of reactive oxygen species to kill cancer cells. Added to this is the ancient hypothesis that light alone can be used to kill cancer cells. 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT) is a therapeutic option for a variety of cutaneous and internal malignancies. PDT uses a photosensitizer that, activated by light in the presence of molecule oxygen, forms ROS, which are responsible for the apoptotic activity of the malignant tissues. 5-ALA is usually used as an endogenous pro-photosensitizer because it is converted to Protoporphyrin IX (PpIX), which enters into the process of heme synthesis and contextually becomes a photosensitizer, radiating a red fluorescent light. In cancer cells, the lack of the ferrochelatase enzyme leads to an accumulation of PpIX and consequently to an increased production of ROS. PDT has the benefit of being administered before or after chemotherapy, radiation, or surgery, without impairing the efficacy of these treatment techniques. Furthermore, sensitivity to PDT is unaffected by the negative effects of chemotherapy or radiation. This review focuses on the studies done so far on 5-ALA-PDT and its efficacy in the treatment of various cancer pathologies.
Topics: Humans; Aminolevulinic Acid; Photosensitizing Agents; Reactive Oxygen Species; Photochemotherapy; Neoplasms; Protoporphyrins; Cell Line, Tumor
PubMed: 37240309
DOI: 10.3390/ijms24108964 -
Journal of Agricultural and Food... Jan 2023A novel photodynamic inactivation (PDI)-mediated antimicrobial film of polylactic acid/5-aminolevulinic acid (PLA/ALA) was successfully fabricated by a covalent grafting...
A novel photodynamic inactivation (PDI)-mediated antimicrobial film of polylactic acid/5-aminolevulinic acid (PLA/ALA) was successfully fabricated by a covalent grafting method using low-temperature plasma. The chemical structure, surface morphology, hydrophilic ability, and mechanical and barrier properties of the films were characterized, and their antibacterial, anti-biofilm potency and preservation effects on ready-to-eat salmon were investigated during storage. Results showed that the amino group of ALA was covalently grafted with the carboxyl group on the surface of PLA after the plasma treatment, with the highest grafting rate reaching ∼50%. The fabricated PLA/ALA films displayed an enhanced barrier ability against water vapor and oxygen. Under blue light-emitting diode illumination, the PLA/ALA films generated massive reactive oxygen species from the endogenous porphyrins in cells induced by ALA and then fatally destroyed the cell wall of planktonic cells and the architectural structures of sessile biofilms of the pathogens ( and ) and spoilage bacterium (). More importantly, the PDI-mediated PLA/ALA films potently inhibited 99.9% native bacteria on ready-to-eat salmon and significantly suppressed the changes of its drip loss, pH, and lipid oxidation (MDA) during storage, and on this basis, the shelf life of salmon was extended by 4 days compared with that of the commercial polyethylene film. Therefore, the PDI-mediated PLA/ALA films are valid in inactivating harmful bacterial and preserving the quality of seafood.
Topics: Animals; Aminolevulinic Acid; Salmon; Polyesters; Seafood; Bacteria; Food Packaging
PubMed: 36548110
DOI: 10.1021/acs.jafc.2c08340