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Der Internist Sep 2021Porphyrias are caused by enzyme defects along the heme biosynthetic pathway. The first line diagnosis of porphyria is based on specific biochemical patterns of elevated...
Porphyrias are caused by enzyme defects along the heme biosynthetic pathway. The first line diagnosis of porphyria is based on specific biochemical patterns of elevated porphyrins and porphyrin precursors in urine, feces, and blood. In clinically active disease accumulated porphyrin precursors and/or porphyrins lead to abdominal, neurologic, psychiatric, endocrine and cardiovascular symptoms, liver damage and/or skin photosensitivity. Porphyrias are classified into acute and nonacute forms. Patients with symptomatic (clinically active) acute hepatic porphyria, e.g. acute intermittent porphyria, porphyria variegata, hereditary coproporphyria, and aminolevulinic acid dehydratase deficiency porphyria, display accumulation of porphyrin precursors, 5‑aminolevulinic acid and porphobilinogen due to regulation disorder. In the non-acute forms of porphyria, such as porphyria cutanea tarda, erythropoietic porphyria, X‑linked protoporphyria and congenital erythropoietic porphyria, accumulated porphyrins lead to skin photosensitivity and occasionally also to severe liver damage. Several different options for treatment, proven and innovative ones, are available for most porphyrias.
Topics: Humans; Porphyria Cutanea Tarda; Porphyria, Acute Intermittent; Porphyrias; Porphyrias, Hepatic; Porphyrins
PubMed: 34185109
DOI: 10.1007/s00108-021-01066-1 -
Theranostics 2021Development of efficient therapeutic strategy to incorporate ultrasound (US)-triggered sonodynamic therapy (SDT) and ferroptosis is highly promising in cancer therapy....
Development of efficient therapeutic strategy to incorporate ultrasound (US)-triggered sonodynamic therapy (SDT) and ferroptosis is highly promising in cancer therapy. However, the SDT efficacy is severely limited by the hypoxia and high glutathione (GSH) in the tumor microenvironment, and ferroptosis is highly associated with reactive oxygen species (ROS) and GSH depletion. A manganese porphyrin-based metal-organic framework (Mn-MOF) was constructed as a nanosensitizer to self-supply oxygen (O) and decrease GSH for enhanced SDT and ferroptosis. and analysis, including characterization, O generation, GSH depletion, ROS generation, lipid peroxidation, antitumor efficacy and tumor immune microenvironment were systematically evaluated. Mn-MOF exhibited catalase-like and GSH decreasing activity . After efficient internalization into cancer cells, Mn-MOF persistently catalyzed tumor-overexpressed HO to produce O to relieve tumor hypoxia and decrease GSH and GPX4, which facilitated the formation of ROS and ferroptosis to kill cancer cells upon US irradiation in hypoxic tumors. Thus, strong anticancer and anti-metastatic activity was found in H22 and 4T1 tumor-bearing mice after a single administration of Mn-MOF upon a single US irradiation. In addition, Mn-MOF showed strong antitumor immunity and improved immunosuppressive microenvironment upon US irradiation by increasing the numbers of activated CD8 T cells and matured dendritic cells and decreaing the numbers of myeloid-derived suppressor cells in tumor tissues. Mn-MOF holds great potential for hypoxic cancer therapy.
Topics: Animals; Apoptosis; Carcinoma, Hepatocellular; Cell Proliferation; Female; Ferroptosis; Glutathione; Humans; Liver Neoplasms; Manganese; Metal-Organic Frameworks; Mice; Mice, Inbred BALB C; Mice, Nude; Porphyrins; Reactive Oxygen Species; Tumor Cells, Cultured; Tumor Hypoxia; Tumor Microenvironment; Ultrasonic Therapy; Xenograft Model Antitumor Assays
PubMed: 33408790
DOI: 10.7150/thno.45511 -
Angewandte Chemie (International Ed. in... Mar 2021Porphyrins and porphyrin derivatives have been widely explored for various applications owing to their excellent photophysical and electrochemical properties. However,... (Review)
Review
Porphyrins and porphyrin derivatives have been widely explored for various applications owing to their excellent photophysical and electrochemical properties. However, inherent shortcomings, such as instability and self-quenching under physiological conditions, limit their biomedical applications. In recent years, metal-organic frameworks (MOFs) have received increasing attention. The construction of porphyrin-based MOFs by introducing porphyrin molecules into MOFs or using porphyrins as organic linkers to form MOFs can combine the unique features of porphyrins and MOFs as well as overcome the limitations of porphyrins. This Review summarizes important synthesis strategies for porphyrin-based MOFs including porphyrin@MOFs, porphyrinic MOFs, and composite porphyrinic MOFs, and highlights recent achievements and progress in the development of porphyrin-based MOFs for biomedical applications in tumor therapy and biosensing. Finally, the challenges and prospects presented by this class of emerging materials for biomedical applications are discussed.
Topics: Animals; Biosensing Techniques; Drug Carriers; Humans; Immunotherapy; Metal-Organic Frameworks; Neoplasms; Photochemotherapy; Photosensitizing Agents; Photothermal Therapy; Porphyrins
PubMed: 31989749
DOI: 10.1002/anie.201909880 -
Molecules (Basel, Switzerland) Apr 2023Details of the structural elucidation of the clinically useful photodynamic therapy sensitizer NPe6 () are presented. NPe6, also designated as Laserphyrin, Talaporfin,... (Review)
Review
Details of the structural elucidation of the clinically useful photodynamic therapy sensitizer NPe6 () are presented. NPe6, also designated as Laserphyrin, Talaporfin, and LS-11, is a second-generation photosensitizer derived from chlorophyll-a, currently used in Japan for the treatment of human lung, esophageal, and brain cancers. After the initial misidentification of the structure of this chlorin-e aspartic acid conjugate as (), NMR and other synthetic procedures described herein arrived at the correct structure (), confirmed using single crystal X-ray crystallography. Interesting new features of chlorin-e chemistry (including the intramolecular formation of an anhydride ()) are reported, allowing chemists to regioselectively conjugate amino acids to each available carboxylic acid on positions 13 (formic), 15 (acetic), and 17 (propionic) of chlorin e (). Cellular investigations of several amino acid conjugates of chlorin-e revealed that the 13-aspartylchlorin-e derivative is more phototoxic than its 15- and 17-regioisomers, in part due to its nearly linear molecular conformation.
Topics: Humans; Photosensitizing Agents; Photochemotherapy; Porphyrins; Amino Acids; Aspartic Acid; Chlorophyllides
PubMed: 37110713
DOI: 10.3390/molecules28083479 -
Molecules (Basel, Switzerland) Jul 2019The synthesis and application of porphyrins has seen a huge shift towards research in porphyrin bio-molecular based systems in the past decade. The preferential... (Review)
Review
The synthesis and application of porphyrins has seen a huge shift towards research in porphyrin bio-molecular based systems in the past decade. The preferential localization of porphyrins in tumors, as well as their ability to generate reactive singlet oxygen and low dark toxicities has resulted in their use in therapeutic applications such as photodynamic therapy. However, their inherent lack of bio-distribution due to water insolubility has shifted research into porphyrin-nanomaterial conjugated systems to address this challenge. This has broadened their bio-applications, viz. bio-sensors, fluorescence tracking, in vivo magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT imaging to photo-immuno-therapy just to highlight a few. This paper reviews the unique theranostic role of porphyrins in disease diagnosis and therapy. The review highlights porphyrin conjugated systems and their applications. The review ends by bringing current challenges and future perspectives of porphyrin based conjugated systems and their respective applications into light.
Topics: Animals; Glycoconjugates; Humans; Magnetic Resonance Imaging; Mice; Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins; Positron-Emission Tomography; Singlet Oxygen; Theranostic Nanomedicine; Water
PubMed: 31340553
DOI: 10.3390/molecules24142669 -
Methods in Molecular Biology (Clifton,... 2023The ommochrome and porphyrin body pigments that give freshwater planarians their brown color are produced by specialized dendritic cells located just beneath the...
The ommochrome and porphyrin body pigments that give freshwater planarians their brown color are produced by specialized dendritic cells located just beneath the epidermis. During embryonic development and regeneration, differentiation of new pigment cells gradually darkens newly formed tissue. Conversely, prolonged light exposure ablates pigment cells through a porphyrin-based mechanism similar to the one that causes light sensitivity in rare human disorders called porphyrias. Here, we describe a novel program using image-processing algorithms to quantify relative pigment levels in live animals and apply this program to analyze changes in bodily pigmentation induced by light exposure. This tool will facilitate further characterization of genetic pathways that affect pigment cell differentiation, ommochrome and porphyrin biosynthesis, and porphyrin-based photosensitivity.
Topics: Animals; Humans; Planarians; Pigmentation; Phenothiazines; Porphyrins
PubMed: 37428383
DOI: 10.1007/978-1-0716-3275-8_16 -
ChemMedChem Aug 2021Photodynamic therapy (PDT) is becoming a promising way to treat various kinds of cancers, with few side effects. Porphyrinoids are the most relevant photosensitizers... (Review)
Review
Photodynamic therapy (PDT) is becoming a promising way to treat various kinds of cancers, with few side effects. Porphyrinoids are the most relevant photosensitizers (PS) in PDT, because they present high extinction coefficients, biocompatibility, and excellent photochemical behavior. To maximize therapeutic effects, polymer-PS conjugates, and PS-loaded nanoparticles have been developed, with insights in improving tumor delivery. However, some drawbacks such as non-biodegradability, multistep fabrication, and low reagent loadings limit their clinical application. A novel strategy, noted by some authors as the "one-for-all" approach, is emerging to circumvent the use of additional delivery agents. This approach relies on the self-assembly of amphiphilic PS to fabricate nanostructures with improved transport properties. In this review we focus on different rational designs of porphyrinoid PS to achieve some of the following attributes in nanoassembly: i) selective uptake, through the incorporation of recognizable biological vectors; ii) responsiveness to stimuli; iii) combination of imaging and therapeutic functions; and iv) multimodal therapy, including photothermal or chemotherapy abilities.
Topics: Antineoplastic Agents; Cell Proliferation; Humans; Molecular Structure; Nanostructures; Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins
PubMed: 33900022
DOI: 10.1002/cmdc.202100201 -
Molecules (Basel, Switzerland) Dec 2022This study presents the spectral characterization of TiO nanoparticles (NPs) functionalized with three porphyrin derivatives: 5,10,15,20-(Tetra-4-aminophenyl) porphyrin...
This study presents the spectral characterization of TiO nanoparticles (NPs) functionalized with three porphyrin derivatives: 5,10,15,20-(Tetra-4-aminophenyl) porphyrin (TAPP), 5,10,15,20-(Tetra-4-methoxyphenyl) porphyrin (TMPP), and 5,10,15,20-(Tetra-4-carboxyphenyl) porphyrin (TCPP). UV-Vis absorption and Fourier transform infrared spectroscopy-attenuated total reflection (FTIR-ATR) spectroscopic studies of these porphyrins and their complexes with TiO NPs were performed. In addition, the efficiency of singlet oxygen generation, the key species in photodynamic therapy, was investigated. UV-Vis absorption spectra of the NPs complexes showed the characteristic bands of porphyrins. These allowed us to determine the loaded porphyrins on TiO NPs functionalized with porphyrins. FTIR-ATR revealed the formation of porphyrin-TiO complexes, suggesting that porphyrin adsorption on TiO may involve the pyrroles in the porphyrin ring, or the radicals of the porphyrin derivative. The quantum yield for singlet oxygen generation by the studied porphyrin complexes with TiO was higher compared to bare porphyrins for TAPP and TMPP, while for the TCPP-TiO NPs complex, a decrease was observed, but still maintained a good efficiency. The TiO NPs conjugates can be promising candidates to be tested in photodynamic therapy in vitro assays.
Topics: Porphyrins; Singlet Oxygen; Photochemotherapy; Spectroscopy, Fourier Transform Infrared; Nanoparticles; Photosensitizing Agents
PubMed: 36615512
DOI: 10.3390/molecules28010318 -
Chemical Research in Toxicology Dec 2022-Methyl protoporphyrin IX (NmePPIX) is a derivative of protoporphyrin IX (PPIX) and the lattice of heme. Certain xenobiotics strongly induce NmePPIX production in the... (Review)
Review
-Methyl protoporphyrin IX (NmePPIX) is a derivative of protoporphyrin IX (PPIX) and the lattice of heme. Certain xenobiotics strongly induce NmePPIX production in the liver. The existence of endogenous NmePPIX in untreated animal liver has also been reported. The detailed mechanisms of NmePPIX biosynthesis remain unclear, but cytochrome P450 enzymes are thought to be critical in xenobiotic-induced NmePPIX production. High levels of NmePPIX cause PPIX accumulation because NmePPIX is a potent inhibitor ( = 7 nM) of ferrochelatase, the last enzyme in the heme biosynthesis pathway that converts PPIX to heme. NmePPIX is also involved in several other physiological processes, including inhibition of nitric oxide production and promotion of lamin aggregation. Compared to the two well-characterized porphyrins, PPIX and heme, NmePPIX is understudied regarding the mechanism of formation, fate, and physiological functions. This Review summarizes the current understanding of NmePPIX and provides perspectives on areas of future research on NmePPIX.
Topics: Animals; Porphyrins; Protoporphyrins; Ferrochelatase; Heme
PubMed: 36459538
DOI: 10.1021/acs.chemrestox.2c00214 -
Molecules (Basel, Switzerland) Jan 2023Despite specialists' efforts to find the best solutions for cancer diagnosis and therapy, this pathology remains the biggest health threat in the world. Global... (Review)
Review
Despite specialists' efforts to find the best solutions for cancer diagnosis and therapy, this pathology remains the biggest health threat in the world. Global statistics concerning deaths associated with cancer are alarming; therefore, it is necessary to intensify interdisciplinary research in order to identify efficient strategies for cancer diagnosis and therapy, by using new molecules with optimal therapeutic potential and minimal adverse effects. This review focuses on studies of porphyrin macrocycles with regard to their structural and spectral profiles relevant to their applicability in efficient cancer diagnosis and therapy. Furthermore, we present a critical overview of the main commercial formulations, followed by short descriptions of some strategies approached in the development of third-generation photosensitizers.
Topics: Humans; Precision Medicine; Porphyrins; Photosensitizing Agents; Neoplasms; Photochemotherapy
PubMed: 36770816
DOI: 10.3390/molecules28031149