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Journal of Materials Chemistry. B Nov 2023Covalent organic frameworks (COFs) have promising applications in enhanced phototherapy. However, COFs that can sustainably play a role in phototherapy without...
Covalent organic frameworks (COFs) have promising applications in enhanced phototherapy. However, COFs that can sustainably play a role in phototherapy without continuous irradiation are extremely scarce. Herein, we report the fabrication of porphyrin-anthracene multifunctional COFs (Por-DPA) for sustainable photosterilization and bacterial-infected wound healing. A porphyrin photosensitizer, as one of the monomers, was used to provide photothermal and photodynamic activities under irradiation. An anthracene derivative, a good chemical source of singlet oxygen (O), was selected as another monomer to capture O and release it continuously cycloreversion in the dark. The prepared Por-DPA COF prevents the self-aggregation quenching of the photosensitizer and thermal damage caused by continuous exposure to external light sources. Besides, Por-DPA exhibits good photothermal conversion performance and efficient O production capacity through dual pathways of photosensitization and cycloreversion. The developed sustainable photosterilization platform not only has good bactericidal effects on and , but also promotes wound healing without obvious side effects, and is expected to be a novel efficient bactericide.
Topics: Photosensitizing Agents; Metal-Organic Frameworks; Porphyrins; Phototherapy; Singlet Oxygen
PubMed: 37987617
DOI: 10.1039/d3tb02017g -
Medicina Clinica Sep 2023
Topics: Humans; Heme; Porphyrias
PubMed: 37827890
DOI: 10.1016/j.medcli.2023.04.037 -
Seminars in Liver Disease Nov 2023The porphyrias are a group of metabolic disorders that are caused by defects in heme biosynthesis pathway enzymes. The result is accumulation of heme precursors, which... (Review)
Review
The porphyrias are a group of metabolic disorders that are caused by defects in heme biosynthesis pathway enzymes. The result is accumulation of heme precursors, which can cause neurovisceral and/or cutaneous photosensitivity. Liver is commonly either a source or target of excess porphyrins, and porphyria-associated hepatic dysfunction ranges from minor abnormalities to liver failure. In this review, the first of a three-part series, we describe the defects commonly found in each of the eight enzymes involved in heme biosynthesis. We also discuss the pathophysiology of the hepatic porphyrias in detail, covering epidemiology, histopathology, diagnosis, and complications. Cellular consequences of porphyrin accumulation are discussed, with an emphasis on oxidative stress, protein aggregation, hepatocellular cancer, and endothelial dysfunction. Finally, we review current therapies to treat and manage symptoms of hepatic porphyria.
Topics: Humans; Rare Diseases; Porphyrins; Porphyrias; Porphyrias, Hepatic; Heme; Liver Neoplasms
PubMed: 37973028
DOI: 10.1055/s-0043-1776760 -
Biomolecules Jul 2023Heme is an iron-containing tetrapyrrole that plays a critical role in various biological processes, including oxygen transport, electron transport, signal transduction,... (Review)
Review
Heme is an iron-containing tetrapyrrole that plays a critical role in various biological processes, including oxygen transport, electron transport, signal transduction, and catalysis. However, free heme is hydrophobic and potentially toxic to cells. Organisms have evolved specific pathways to safely transport this essential but toxic macrocycle within and between cells. The bacterivorous soil-dwelling nematode is a powerful animal model for studying heme-trafficking pathways, as it lacks the ability to synthesize heme but instead relies on specialized trafficking pathways to acquire, distribute, and utilize heme. Over the past 15 years, studies on this microscopic animal have led to the identification of a number of heme-trafficking proteins, with corresponding functional homologs in vertebrates. In this review, we provide a comprehensive overview of the heme-trafficking proteins identified in and their corresponding homologs in related organisms.
Topics: Animals; Caenorhabditis elegans; Heme; Homeostasis; Nematoda; Biological Transport
PubMed: 37509184
DOI: 10.3390/biom13071149 -
Advanced Science (Weinheim,... Nov 2023Choroidal neovascularization (CNV) is the key pathological event of wet age-related macular degeneration (wAMD) leading to irreversible vision loss. Currently,...
Choroidal neovascularization (CNV) is the key pathological event of wet age-related macular degeneration (wAMD) leading to irreversible vision loss. Currently, anti-angiogenic therapy with anti-vascular endothelial growth factor (VEGF) agents has become the standard treatment for wAMD, while it is still subject to several limitations, including the safety concerns of monthly intravitreal administration and insufficient efficacy for neovascular occlusion. Combined therapy with photodynamic therapy (PDT) and anti-angiogenic agents has emerged as a novel treatment paradigm. Herein, a novel and less-invasive approach is reported to achieve anti-angiogenic and photodynamic combination therapy of wAMD by intravenous administration of a photoactivatable nanosystem (Di-DAS-VER NPs). The nanosystem is self-assembled by reactive oxygen species (ROS)-sensitive dasatinib (DAS) prodrug and photosensitizer verteporfin (VER). After red-light irradiation to the diseased eyes, intraocular release of anti-angiogenic DAS is observed, together with selective neo-vessels occlusion by VER-generated ROS. Notably, Di-DAS-VER NPs demonstrates promising therapeutic efficacy against CNV with minimized systemic toxicity. The study enables an efficient intravenous wAMD therapy by integrating a photoactivation process with combinational therapeutics into one simple nanosystem.
Topics: Humans; Reactive Oxygen Species; Porphyrins; Photochemotherapy; Verteporfin; Macular Degeneration; Choroidal Neovascularization
PubMed: 37705491
DOI: 10.1002/advs.202301985 -
Biomaterials Science May 2024Covalent organic frameworks (COFs) constitute a class of highly functional porous materials composed of lightweight elements interconnected by covalent bonds,... (Review)
Review
Covalent organic frameworks (COFs) constitute a class of highly functional porous materials composed of lightweight elements interconnected by covalent bonds, characterized by structural order, high crystallinity, and large specific surface area. The integration of naturally occurring porphyrin molecules, renowned for their inherent rigidity and conjugate planarity, as building blocks in COFs has garnered significant attention. This strategic incorporation addresses the limitations associated with free-standing porphyrins, resulting in the creation of well-organized porous crystal structures with molecular-level directional arrangements. The unique optical, electrical, and biochemical properties inherent to porphyrin molecules endow these COFs with diversified applications, particularly in the realm of biology. This review comprehensively explores the synthesis and modulation strategies employed in the development of porphyrin-based COFs and delves into their multifaceted applications in biological contexts. A chronological depiction of the evolution from design to application is presented, accompanied by an analysis of the existing challenges. Furthermore, this review offers directional guidance for the structural design of porphyrin-based COFs and underscores their promising prospects in the field of biology.
Topics: Porphyrins; Metal-Organic Frameworks; Humans; Porosity; Animals
PubMed: 38717456
DOI: 10.1039/d4bm00214h -
Journal of Materials Chemistry. B Jul 2023Porphyrins are naturally occurring organic molecules that have attracted widespread attention for their potential in the field of biomedical research. Porphyrin-based... (Review)
Review
Porphyrins are naturally occurring organic molecules that have attracted widespread attention for their potential in the field of biomedical research. Porphyrin-based metal-organic frameworks (MOFs) that utilize porphyrin molecules as organic ligands have gained attention from researchers due to their excellent results as photosensitizers in tumor photodynamic therapy (PDT). Additionally, MOFs hold significant promise and potential for other tumor therapeutic approaches due to their tunable size and pore size, excellent porosity, and ultra-high specific surface area. Active delivery of nanomaterials targeted molecules for tumor therapy has demonstrated greater accumulation, lower drug doses, higher therapeutic efficacy, and reduced side effects relative to passive targeting through the enhanced permeation and retention effect (EPR). This paper presents a comprehensive review of the targeting methods employed by porphyrin-based MOFs in tumor targeting therapy over the past few years. It further discusses the applications of porphyrin-based MOFs for targeted cancer therapy through various therapeutic methods. The objective of this paper is to provide a valuable reference and source of ideas for targeted therapy using porphyrin-based MOF materials and to inspire further exploration of their potential in the field of cancer therapy.
Topics: Humans; Metal-Organic Frameworks; Porphyrins; Neoplasms; Photosensitizing Agents; Drug Delivery Systems
PubMed: 37305964
DOI: 10.1039/d3tb00632h -
Biotechnology and Bioengineering Dec 2023Cytochrome P450s belong to a family of heme-binding monooxygenases, which catalyze regio- and stereospecific functionalisation of C-H, C-C, and C-N bonds, including... (Review)
Review
Cytochrome P450s belong to a family of heme-binding monooxygenases, which catalyze regio- and stereospecific functionalisation of C-H, C-C, and C-N bonds, including heteroatom oxidation, oxidative C-C bond cleavages, and nitrene transfer. P450s are considered useful biocatalysts for the production of pharmaceutical products, fine chemicals, and bioremediating agents. Despite having tremendous biotechnological potential, being heme-monooxygenases, P450s require either autologous or heterologous redox partner(s) to perform chemical transformations. Randomly distributed P450s throughout a bacterial genome and devoid of particular redox partners in natural products biosynthetic gene clusters (BGCs) showed an extra challenge to reveal their pharmaceutical potential. However, continuous efforts have been made to understand their involvement in antibiotic biosynthesis and their modification, and this review focused on such BGCs. Here, particularly, we have discussed the role of P450s involved in the production of macrolides and aminocoumarin antibiotics, nonribosomal peptide (NRPSs) antibiotics, ribosomally synthesized and post-translationally modified peptide (RiPPs) antibiotics, and others. Several reactions catalyzed by P450s, as well as the role of their redox partners involved in the BGCs of various antibiotics and their derivatives, have been primarily addressed in this review, which would be useful in further exploration of P450s for the biosynthesis of new therapeutics.
Topics: Cytochrome P-450 Enzyme System; Oxidation-Reduction; Biocatalysis; Heme; Peptides
PubMed: 37691185
DOI: 10.1002/bit.28548 -
ACS Sensors Oct 2023The ability to monitor intracellular calcium concentrations using fluorescent probes has led to important insights into biological signaling processes at the cellular...
The ability to monitor intracellular calcium concentrations using fluorescent probes has led to important insights into biological signaling processes at the cellular level. An important challenge is to relate such measurements to broader patterns of signaling across fields of view that are inaccessible to optical techniques. To meet this need, we synthesized molecular probes that couple calcium-binding moieties to lanthanide texaphyrins, resulting in complexes endowed with a diverse complement of magnetic and photophysical properties. We show that the probes permit intracellular calcium levels to be assessed by fluorescence, photoacoustic, and magnetic resonance imaging modalities and that they are detectable by multimodal imaging in brain tissue. This work thus establishes a route for monitoring signaling processes over a range of spatial and temporal scales.
Topics: Calcium; Porphyrins; Magnetic Resonance Imaging; Multimodal Imaging
PubMed: 37812688
DOI: 10.1021/acssensors.3c01387 -
Advanced Science (Weinheim,... May 2024Photoacoustic imaging (PAI)-guided photothermal therapy (PTT) in the second near-infrared (NIR-II, 1000-1700 nm) window has been attracting attention as a promising...
Photoacoustic imaging (PAI)-guided photothermal therapy (PTT) in the second near-infrared (NIR-II, 1000-1700 nm) window has been attracting attention as a promising cancer theranostic platform. Here, it is reported that the π-extended porphyrins fused with one or two nanographene units (NGP-1 and NGP-2) can serve as a new class of NIR-responsive organic agents, displaying absorption extending to ≈1000 and ≈1400 nm in the NIR-I and NIR-II windows, respectively. NGP-1 and NGP-2 are dispersed in water through encapsulation into self-assembled nanoparticles (NPs), achieving high photothermal conversion efficiency of 60% and 69%, respectively, under 808 and 1064 nm laser irradiation. Moreover, the NIR-II-active NGP-2-NPs demonstrated promising photoacoustic responses, along with high photostability and biocompatibility, enabling PAI and efficient NIR-II PTT of cancer in vivo.
Topics: Porphyrins; Theranostic Nanomedicine; Photoacoustic Techniques; Mice; Animals; Nanoparticles; Graphite; Humans; Infrared Rays; Disease Models, Animal; Photothermal Therapy; Cell Line, Tumor; Neoplasms; Phototherapy
PubMed: 38430537
DOI: 10.1002/advs.202309131