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Annual Review of Medicine Jan 2024The porphyrias are a group of rare diseases, each resulting from a defect in a different enzymatic step of the heme biosynthetic pathway. They can be broadly divided... (Review)
Review
The porphyrias are a group of rare diseases, each resulting from a defect in a different enzymatic step of the heme biosynthetic pathway. They can be broadly divided into two categories, hepatic and erythropoietic porphyrias, depending on the primary site of accumulation of heme intermediates. These disorders are multisystemic with variable symptoms that can be encountered by physicians in any specialty. Here, we review the porphyrias and describe their clinical presentation, diagnosis, and management. We discuss novel therapies that are approved or in development. Early diagnosis is key for the appropriate management and prevention of long-term complications in these rare disorders.
Topics: Humans; Porphyrias; Heme
PubMed: 37540847
DOI: 10.1146/annurev-med-042921-123602 -
Pharmacology & Therapeutics Aug 2023Protoporphyrin IX (PPIX) is an intermediate in the heme biosynthesis pathway. Abnormal accumulation of PPIX due to certain pathological conditions such as erythropoietic... (Review)
Review
Protoporphyrin IX (PPIX) is an intermediate in the heme biosynthesis pathway. Abnormal accumulation of PPIX due to certain pathological conditions such as erythropoietic protoporphyria and X-linked protoporphyria causes painful phototoxic reactions of the skin, which can significantly impact daily life. Endothelial cells in the skin have been proposed as the primary target for PPIX-induced phototoxicity through light-triggered generation of reactive oxygen species. Current approaches for the management of PPIX-induced phototoxicity include opaque clothing, sunscreens, phototherapy, blood therapy, antioxidants, bone marrow transplantation, and drugs that increase skin pigmentation. In this review, we discuss the present understanding of PPIX-induced phototoxicity including PPIX production and disposition, conditions that lead to PPIX accumulation, symptoms and individual differences, mechanisms, and therapeutics.
Topics: Humans; Endothelial Cells; Protoporphyrins; Protoporphyria, Erythropoietic; 5-Aminolevulinate Synthetase
PubMed: 37392940
DOI: 10.1016/j.pharmthera.2023.108487 -
International Journal of Molecular... Oct 2023The luminescent and photophysical properties of the etioporphyrin-I complex with indium(III) chloride, InCl-EtioP-I were experimentally studied at room and liquid...
The luminescent and photophysical properties of the etioporphyrin-I complex with indium(III) chloride, InCl-EtioP-I were experimentally studied at room and liquid nitrogen temperatures in pure and mixed toluene solutions. At 77 K, in a 1:2 mixture of toluene with diethyl ether, the quantum yield of phosphorescence reaches 10.2%, while the duration of phosphorescence is 17 ms. At these conditions, the ratio of phosphorescence-to-fluorescence integral intensities is equal to 26.1, which is the highest for complexes of this type. At 298 K, the quantum yield of the singlet oxygen generation is maximal in pure toluene (81%). Quantum-chemical calculations of absorption and fluorescence spectra at temperatures of 77 K and 298 K qualitatively coincide with the experimental data. The InCl-EtioP-I compound will further be used as a photoresponsive material in thin-film optoelectronic devices.
Topics: Luminescence; Etioporphyrins; Chlorides; Spectrometry, Fluorescence; Toluene
PubMed: 37894849
DOI: 10.3390/ijms242015168 -
Trends in Immunology Aug 2023PANoptosomes are large cell death-inducing complexes that drive a type of cell death called PANoptosis during infection and inflammation. Sundaram and colleagues...
PANoptosomes are large cell death-inducing complexes that drive a type of cell death called PANoptosis during infection and inflammation. Sundaram and colleagues recently identified NLRP12 as a PANoptosome that induces PANoptosis in response to heme, TNF, and pathogen-associated molecular patterns (PAMPs), indicating a role for NLRP12 in hemolytic and inflammatory diseases.
Topics: Humans; Intracellular Signaling Peptides and Proteins; Heme; Inflammation
PubMed: 37423881
DOI: 10.1016/j.it.2023.06.008 -
Molecular Pharmaceutics Nov 2023The aim of this study is to evaluate a radioactive metal complex platform for brain tumor targeting. Herein, we introduce a new porphyrin derivative,...
The aim of this study is to evaluate a radioactive metal complex platform for brain tumor targeting. Herein, we introduce a new porphyrin derivative, 5,10,15,20-(tetra-,-dimethyl-4-aminophenyl)porphyrin (TDAP), in which four ,-dimethyl-4--phenylenediamine (DMPD) moieties are conjugated to the porphyrin labeled with the radiometal Cu. DMPD affected the pharmacokinetics of porphyrin in terms of retention time in vivo and tumor-targeting ability relative to those of unmodified porphyrin. [Cu]Cu-TDAP showed stronger enhancement than [Cu]Cu-porphyrin in U87MG glioblastoma cells, especially in the cytoplasm and nucleus, indicating its tumor-targeting properties and potential use as a therapeutic agent. In the subcutaneous and orthotopic models of brain-tumor-bearing mice, [Cu]Cu-TDAP was clearly visualized in the tumor site via positron emission tomography imaging and showed a tumor-to-brain ratio as high as 13. [Cu]Cu-TDAP deserves attention as a new diagnostic agent that is suitable for the early diagnosis and treatment of brain tumors.
Topics: Animals; Mice; Porphyrins; Cell Line, Tumor; Copper Radioisotopes; Brain Neoplasms; Glioblastoma
PubMed: 37851927
DOI: 10.1021/acs.molpharmaceut.3c00704 -
Journal of Inorganic Biochemistry Jan 2024
Topics: Heme
PubMed: 37953207
DOI: 10.1016/j.jinorgbio.2023.112423 -
Journal of Materials Chemistry. B Jul 2023Porphyrins and their derivatives have excellent photophysical and electrochemical properties, which have attracted great interest in the fields of catalysis, biosensing,... (Review)
Review
Porphyrins and their derivatives have excellent photophysical and electrochemical properties, which have attracted great interest in the fields of catalysis, biosensing, gas storage, solar cells, biomedicine, However, the inherent limitations, such as self-quenching, weak absorption at biological spectral windows and poor photochemical stability, severely hinder their applications in biomedicine, especially in the field of photodynamic therapy (PDT). In recent years, metal-organic frameworks (MOFs) have received increasing attention as a class of hybrid porous coordination polymers assembled from metal ions/secondary building units (SBUs) and organic linkers. By introducing porphyrins into MOFs the encapsulation in the pores as well as grafting on the surface to form porphyrin@MOFs or using porphyrins as organic linkers to construct porphyrin-MOFs, not only the unique properties of porphyrins and MOFs are combined, but also the limitations of porphyrins are overcome and their applications are facilitated in the biomedicine field. This article reviews important synthetic strategies of forming porphyrin-based MOFs (including porphyrin@MOFs and porphyrin-MOFs), which focuses on the recent research achievements and progress in PDT and tumor therapy fields. Furthermore, by carefully designing the composition of MOFs (such as the modification of organic linkers), MOFs could respond to the tumor microenvironment for on-demand treatment. In addition, some other strategies, including chemotherapy, photothermal therapy (PTT) and the latest cancer immunotherapy, are also combined in the review. Finally, the challenges and prospects in biomedical applications of this class of emerging materials are discussed.
Topics: Metal-Organic Frameworks; Porphyrins; Photochemotherapy; Drug Carriers; Catalysis
PubMed: 37310273
DOI: 10.1039/d2tb02789e -
Annual Review of Medicine Jan 2024Carbon monoxide (CO) poisoning leads to 50,000-100,000 emergency room visits and 1,500-2,000 deaths each year in the United States alone. Even with treatment, survivors... (Review)
Review
Carbon monoxide (CO) poisoning leads to 50,000-100,000 emergency room visits and 1,500-2,000 deaths each year in the United States alone. Even with treatment, survivors often suffer from long-term cardiac and neurocognitive deficits, highlighting a clear unmet medical need for novel therapeutic strategies that reduce morbidity and mortality associated with CO poisoning. This review examines the prevalence and impact of CO poisoning and pathophysiology in humans and highlights recent advances in therapeutic strategies that accelerate CO clearance and mitigate toxicity. We focus on recent developments of high-affinity molecules that take advantage of the uniquely strong interaction between CO and heme to selectively bind and sequester CO in preclinical models. These scavengers, which employ heme-binding scaffolds ranging from organic small molecules to hemoproteins derived from humans and potentially even microorganisms, show promise as field-deployable antidotes that may rapidly accelerate CO clearance and improve outcomes for survivors of acute CO poisoning.
Topics: Humans; United States; Carbon Monoxide Poisoning; Heme
PubMed: 37582490
DOI: 10.1146/annurev-med-052422-020045 -
ChemMedChem Dec 2023Photodynamic therapy (PDT) efficiently induces apoptosis through visible-light irradiation of photosensitizers (PSs) within tumors and microbial cells. Porphyrin... (Review)
Review
Photodynamic therapy (PDT) efficiently induces apoptosis through visible-light irradiation of photosensitizers (PSs) within tumors and microbial cells. Porphyrin analogues serve as widely utilized photosensitizing agents with their therapeutic abilities being governed by molecular structures and central metal ions. However, these macrocyclic compounds tend to agglutinate and form stacks in aqueous environments, resulting in a loss of photochemical activity. To overcome this limitation, encapsulation within liposomes and polymer micelles enables the dispersion of porphyrins as monomolecular entities in aqueous solutions, preventing undesirable deactivation. Recently, the use of reconstituted hemoproteins containing various metal-porphyrins and protein cages incorporating porphyrins has garnered significant interest as a new generation of biocompatible PSs. In this concept paper, we provide a comprehensive review of recent developments and trends of protein-porphyrin complex PSs for applications in anticancer and antimicrobial PDTs.
Topics: Photosensitizing Agents; Porphyrins; Photochemotherapy; Light; Anti-Infective Agents
PubMed: 37821798
DOI: 10.1002/cmdc.202300373 -
Biomedicine & Pharmacotherapy =... Aug 2023Photodynamic therapy (PDT) and sonodynamic therapy (SDT) are non-invasive treatment methods with obvious inhibitory effect on tumors and have few side effects, which... (Review)
Review
Photodynamic therapy (PDT) and sonodynamic therapy (SDT) are non-invasive treatment methods with obvious inhibitory effect on tumors and have few side effects, which have been widely concerned and explored by researchers. Sensitizer is the main factor in determining the therapeutic effect of PDT and SDT. Porphyrins, a group of organic compounds widespread in nature, can be activated by light or ultrasound and produce reactive oxygen species. Therefore, porphyrins as sensitizers in PDT have been widely explored and investigated for many years. Herein, we summarize the classical porphyrin compounds and their applications and mechanisms in PDT and SDT. The application of porphyrin in clinical diagnosis and imaging is also discussed. In conclusion, porphyrins have good application prospects in disease treatment as an important part of PDT or SDT, and in clinical diagnosis and imaging.
Topics: Humans; Porphyrins; Photochemotherapy; Ultrasonic Therapy; Neoplasms; Reactive Oxygen Species
PubMed: 37236030
DOI: 10.1016/j.biopha.2023.114933