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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 -
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) 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 -
Anais Da Academia Brasileira de Ciencias 2018This review has two parts. The first one gives an approach to interdisciplinary studies against cancer carried out by many scientists using porphyrin-type substrates as... (Review)
Review
This review has two parts. The first one gives an approach to interdisciplinary studies against cancer carried out by many scientists using porphyrin-type substrates as photosensitizers in PDT. Intensive studies were performed for almost six decades. The successes really started in 1993 with the first formulation patented under the trade name Photofrin, which was immediately approved in several countries to treat certain types of cancer. Photofrin is still used although certain negative features soon became well known. That has motivated the search for better new photosensitizers. Several ones were developed, evaluated and a few of them had clinical approval. This group includes porphyrin derivatives and pro-drugs (aminolevulinic acid and its alkyl esters). Oncological, dermatological and ophthalmic applications are now taking place for the benefit of mankind. The second part of this review is related with the work carried out in Aveiro at the authors University on the synthesis and biological evaluation of several potential PDT photosensitizers. Not only new synthetic methodologies mainly for porphyrins and chlorins were developed but also other related macrocycles of the phthalocyanine and corrole types have entered in the same "pipeline". In vivo and in vitro biological evaluations also took place under interdisciplinary studies.
Topics: Humans; Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins
PubMed: 29873666
DOI: 10.1590/0001-3765201820170811 -
Journal of Liposome Research 2015Porphyrin-lipid nanovesicles (PLN) have been developed with intrinsic capabilities as activatable multimodal photonic contrast agents. Radiolabeling of PLN encapsulating...
Porphyrin-lipid nanovesicles (PLN) have been developed with intrinsic capabilities as activatable multimodal photonic contrast agents. Radiolabeling of PLN encapsulating drugs could eventually be able to provide quantitative in vivo information for diagnosing and treating diseases. In this study, we developed (99m)Tc-labeled porphyrin-lipid nanovesicles ((99m)Tc-PLN) as a cargo-encapsulated formulation without significant impact on liposome integrity and encapsulation stability. 50 mM calcein was encapsulated into PLN by probe sonication. The size of the PLN was about 150 nm. The PLN were then reacted with (99m)Tc using SnCl2 dissolved in 1 mM HCl as a reducing agent and incubated for 10 min at 22 °C. The radiolabeling efficiency and stability of (99m)Tc-PLN were evaluated by instant thin-layer chromatography and low-pressure liquid chromatography (LPLC). (99m)Tc labeling was successful with a >92% labeling efficiency. LPLC showed that the liposomal elution peaks of the porphyrin-lipid and the calcein overlapped with the radioactivity elution peak of (99m)Tc-labeled PLN. The (99m)Tc-labeling procedure did not change the size of PLN. Encapsulated calcein remained inert inside PLN. Thus, this work lays out a simple and effective radiolabeling method using SnCl2 in HCl in the preparation of (99m)Tc-PLN.
Topics: Lipids; Nanostructures; Porphyrins; Technetium
PubMed: 24963601
DOI: 10.3109/08982104.2014.932379 -
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 -
Chemistry (Weinheim An Der Bergstrasse,... Sep 2015Silylation of peripherally lithiated porphyrins with silyl electrophiles has realized the first synthesis of a series of directly silyl-substituted porphyrins. The...
Silylation of peripherally lithiated porphyrins with silyl electrophiles has realized the first synthesis of a series of directly silyl-substituted porphyrins. The meso-silyl group underwent facile protodesilylation, whereas the β-silyl group was entirely compatible with standard work-up and purification on silica gel. The meso-silyl group caused larger substituent effects to the porphyrin compared with the β-silyl group. Silylation of β-lithiated porphyrins with 1,2-dichlorodisilane furnished β-to-β disilane-bridged porphyrin dimers. A doubly β-to-β disilane-bridged Ni(II)-porphyrin dimer was also synthesized from a β,β-dilithiated Ni(II)-porphyrin and characterized by X-ray crystallographic analysis to take a steplike structure favorable for interporphyrinic interaction. Denickelation of β-silylporphyrins was achieved upon treatment with a 4-tolylmagnesium bromide to yield the corresponding freebase porphyrins.
Topics: Crystallography, X-Ray; Metalloporphyrins; Molecular Structure; Nickel; Porphyrins; Silanes
PubMed: 26356498
DOI: 10.1002/chem.201502563