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Angewandte Chemie (International Ed. in... Jun 2022We report a cationic porphyrin 5,10,15,20-tetrakis-(4-N-methylpyridyl)-porphyrin (TMPyP) that can respond to specific bacteria, followed by adaptable...
We report a cationic porphyrin 5,10,15,20-tetrakis-(4-N-methylpyridyl)-porphyrin (TMPyP) that can respond to specific bacteria, followed by adaptable photodynamic/photothermal therapy processes. TMPyP could be reduced to phlorin by facultative anaerobes with a strong reducing ability such as E. coli and S. typhimurium in hypoxic environments, possessing strong NIR absorption and remarkable photothermal conversion capacity, thus demonstrating excellent antimicrobial activity (>99 %) by photothermal therapy. While in an aerobic environment with aerobic bacteria, TMPyP functioned as a typical photosensitizer that killed bacteria effectively (>99.9 %) by photodynamic therapy. By forming a host-guest complex with cucurbit[7]uril, the biocompatibility of TMPyP significantly improved. This kind of bacteria-responsive porphyrin shows specificity and adaptivity in antimicrobial treatment and holds potential in non-invasive treatments of bacterial infections.
Topics: Anti-Infective Agents; Bacteria; Escherichia coli; Photochemotherapy; Photosensitizing Agents; Photothermal Therapy; Porphyrins
PubMed: 35332634
DOI: 10.1002/anie.202200799 -
Genome Biology Dec 2022G-quadruplexes (G4s) are unique noncanonical nucleic acid secondary structures, which have been proposed to physically interact with transcription factors and chromatin...
BACKGROUND
G-quadruplexes (G4s) are unique noncanonical nucleic acid secondary structures, which have been proposed to physically interact with transcription factors and chromatin remodelers to regulate cell type-specific transcriptome and shape chromatin landscapes.
RESULTS
Based on the direct interaction between G4 and natural porphyrins, we establish genome-wide approaches to profile where the iron-liganded porphyrin hemin can bind in the chromatin. Hemin promotes genome-wide G4 formation, impairs transcription initiation, and alters chromatin landscapes, including decreased H3K27ac and H3K4me3 modifications at promoters. Interestingly, G4 status is not involved in the canonical hemin-BACH1-NRF2-mediated enhancer activation process, highlighting an unprecedented G4-dependent mechanism for metabolic regulation of transcription. Furthermore, hemin treatment induces specific gene expression profiles in hepatocytes, underscoring the in vivo potential for metabolic control of gene transcription by porphyrins.
CONCLUSIONS
These studies demonstrate that G4 functions as a sensor for natural porphyrin metabolites in cells, revealing a G4-dependent mechanism for metabolic regulation of gene transcription and chromatin landscapes, which will deepen our knowledge of G4 biology and the contribution of cellular metabolites to gene regulation.
Topics: G-Quadruplexes; Chromatin; Hemin; Porphyrins; Transcription, Genetic
PubMed: 36522639
DOI: 10.1186/s13059-022-02830-8 -
Biomaterials Science May 2022The emergence of antibiotic drug resistance has undermined the efficacy of antibiotics, and is becoming a severe threat to public health. To combat antibiotic drug...
The emergence of antibiotic drug resistance has undermined the efficacy of antibiotics, and is becoming a severe threat to public health. To combat antibiotic drug resistance and to replace traditional antibiotic treatment, an alternative strategy based on antibacterial photodynamic therapy (APDT), which has broad applicability, high efficiency and less potential of developing antibiotic drug resistance, has been developed. In this work, the cationic porphyrin-based nanoparticles (NPs) were prepared by epoxy-amine chain extension polymerization of diepoxy-terminated poly(ethylene glycol) (PEG) and tetraamino-containing porphyrin, followed by quaternization with methyl iodine and butyl bromide. The as-obtained cationic porphyrin NPs preserved the photophysical properties of porphyrin derivatives, and can efficiently generate singlet oxygen (O) under 635 nm laser irradiation. The cationic porphyrin-based NPs displayed intrinsic antibacterial properties, and exhibited strong APDT effect on Gram-positive bacteria by destroying the bacterial cell membranes. Upon incubation with different bacterial strains, it was found that they could be utilized to identify Gram-positive bacteria by observing the sedimentation behavior of their mixtures, and visualizing their co-cultured and centrifugal bacteria cakes. In addition, the cationic porphyrin-based NPs had good hemocompatibility and low dark cytotoxicity.
Topics: Anti-Bacterial Agents; Cations; Gram-Positive Bacteria; Nanoparticles; Photochemotherapy; Photosensitizing Agents; Porphyrins
PubMed: 35522076
DOI: 10.1039/d2bm00265e -
Life Science Alliance Jul 2024All cancer cells reprogram metabolism to support aberrant growth. Here, we report that cancer cells employ and depend on imbalanced and dynamic heme metabolic pathways,...
All cancer cells reprogram metabolism to support aberrant growth. Here, we report that cancer cells employ and depend on imbalanced and dynamic heme metabolic pathways, to accumulate heme intermediates, that is, porphyrins. We coined this essential metabolic rewiring "porphyrin overdrive" and determined that it is cancer-essential and cancer-specific. Among the major drivers are genes encoding mid-step enzymes governing the production of heme intermediates. CRISPR/Cas9 editing to engineer leukemia cell lines with impaired heme biosynthetic steps confirmed our whole-genome data analyses that porphyrin overdrive is linked to oncogenic states and cellular differentiation. Although porphyrin overdrive is absent in differentiated cells or somatic stem cells, it is present in patient-derived tumor progenitor cells, demonstrated by single-cell RNAseq, and in early embryogenesis. In conclusion, we identified a dependence of cancer cells on non-homeostatic heme metabolism, and we targeted this cancer metabolic vulnerability with a novel "bait-and-kill" strategy to eradicate malignant cells.
Topics: Humans; Heme; Porphyrins; Cell Line, Tumor; CRISPR-Cas Systems; Neoplasms; Metabolic Networks and Pathways; Cell Differentiation; Gene Editing; Animals; Mice
PubMed: 38649187
DOI: 10.26508/lsa.202302547 -
Dalton Transactions (Cambridge, England... Apr 2023Photodynamic therapy (PDT) is a mode of treatment for different types of cancers, which involves a nontoxic photosensitizer (PS), a light source to activate the PS, and... (Review)
Review
Photodynamic therapy (PDT) is a mode of treatment for different types of cancers, which involves a nontoxic photosensitizer (PS), a light source to activate the PS, and ground-state molecular oxygen (O). Light activation of the PS leads to the generation of reactive oxygen species (ROS), which initiates a toxic effect on the surrounding cellular substrates, thereby destroying the cancerous cells. The commercially used PDT drug Photofrin which is a tetrapyrrolic porphyrin-based photosensitizer has drawbacks such as aggregation in water, prolonged skin photosensitivity, variability in chemical compositions, and minimal absorbance in the red-light region. Metallation of the porphyrin core with diamagnetic metal ions aids the photogeneration of singlet oxygen (ROS). Metalating with Sn(IV) provides a six-coordination octahedral geometry with -diaxial ligands. This approach suppresses aggregation in aqueous media and increases ROS generation upon light exposure due to the heavy atom effect. Bulky -diaxial ligation hinders the approach of the Sn(IV) porphyrins, thereby suppressing aggregation effects. In this review, we document the recently reported Sn(IV) porphyrinoids and their photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) activity properties. In a similar manner to PDT, the photosensitizer is used to kill the bacteria upon irradiation with light during PACT. Often, bacteria develop resistance against conventional chemotherapeutic drugs over time, decreasing their antibacterial properties. However, in the case of PACT, it is difficult to generate resistance against singlet oxygen produced by the photosensitizer.
Topics: Photosensitizing Agents; Photochemotherapy; Reactive Oxygen Species; Singlet Oxygen; Anti-Infective Agents; Porphyrins; Bacteria; Water
PubMed: 37009934
DOI: 10.1039/d3dt00603d -
Journal of Hazardous Materials Oct 2022A nitrogen (N), oxygen (O)-rich porphyrin-based covalent organic framework (COF), in which interlayer porphyrin molecules are vertically stacked, is prepared and...
A nitrogen (N), oxygen (O)-rich porphyrin-based covalent organic framework (COF), in which interlayer porphyrin molecules are vertically stacked, is prepared and characterized. As-prepared N,O-rich TpTph COF shows a high adsorption capacity for Cd due to the abundant coordination sites. More interesting, it is found that the formation of COF enlarges the porphyrin ring center space, thus facilitating the Cdcoordination, and the resulting optical signal changes make the ratiometric detection of Cd possible. Furthermore, using carbon fiber (CF) filaments, which are obtained from low cost and easy-to-obtain actived carbon mask, as support, porphyrin COF-based CF@TpTph membrane is prepared through in-situ growth of COF on the support followed by simple mechanical pressing. The CF@TpTph membrane is demonstrated to work well for both Cd removal and enrichment from soil and water samples, and shows the advantages of ease of handling, robust stability, reduced secondary pollution risk to samples, and good reusability. This work provides a powerful tool for Cd removal and enrichment, exhibits that preparing porphyrin-based COFs is a feasible way to promote the interactions between porphyrin ring and Cd, and demonstrates that mechanical pressing is a promising strategy for the design of COF-based monolithic materials to promote the practical applications of COFs.
Topics: Adsorption; Cadmium; Carbon Fiber; Metal-Organic Frameworks; Porphyrins
PubMed: 35853339
DOI: 10.1016/j.jhazmat.2022.129574 -
ACS Applied Bio Materials Dec 2023This study presents the synthesis and characterization of monosubstituted cationic porphyrin as a photodynamic therapeutic agent. Cationic porphyrin was converted into...
This study presents the synthesis and characterization of monosubstituted cationic porphyrin as a photodynamic therapeutic agent. Cationic porphyrin was converted into ionic materials by using a single-step ion exchange reaction. The small iodide counteranion was replaced with bulky BETI and IR783 anions to reduce aggregation and enhance the photodynamic effect of porphyrin. Carrier-free ionic nanomedicines were then prepared by using the reprecipitation method. The photophysical characterization of parent porphyrin, ionic materials, and ionic nanomaterials, including absorbance, fluorescence and phosphorescence emission, quantum yield, radiative and nonradiative rate, and lifetimes, was performed. The results revealed that the counteranion significantly affects the photophysical properties of porphyrin. The ionic nanomaterials exhibited an increase in the reactive oxygen yield and enhanced cytotoxicity toward the MCF-7 cancer cell line. Examination of results revealed that the ionic materials exhibited an enhanced photodynamic therapeutic activity with a low IC value (nanomolar) in cancerous cells. These nanomedicines were mainly localized in the mitochondria. The improved light cytotoxicity is attributed to the enhanced photophysical properties and positive surface charge of the ionic nanomedicines that facilitate efficient cellular uptake. These results demonstrate that ionic material-based nanodrugs are promising photosensitizers for photodynamic therapy.
Topics: Humans; Porphyrins; Nanomedicine; Photochemotherapy; Photosensitizing Agents; Cations
PubMed: 38063308
DOI: 10.1021/acsabm.3c00809 -
Chemical Society Reviews Nov 2022Half a century after the synthesis of the first subporphyrinoid, the study of tripyrrole and trisoindole porphyrin analogues constitutes a fervent and rapidly expanding... (Review)
Review
Half a century after the synthesis of the first subporphyrinoid, the study of tripyrrole and trisoindole porphyrin analogues constitutes a fervent and rapidly expanding research area. The outstanding structural, electronic and optical features of these cone-shaped aromatic macrocycles render them attractive candidates for a wide variety of applications, ranging from optoelectronics to biomedicine. To tune their properties and exploit their functionalities, the development of novel methodologies for the synthesis and post-functionalization of these contracted porphyrinoids, as well as a deep understanding of their supramolecular organization and their implementation into multicomponent systems of increasing complexity are of paramount importance. Herein, a review of the most recent advances in the fundamentals and applications of subporphyrinoids is presented, which comprehensively cover the last decade of discoveries. The final aim is to highlight the chemical versatility and intriguing physicochemical features of subporphyrinoids, while providing an updated overview of their most promising applications.
Topics: Porphyrins
PubMed: 36354343
DOI: 10.1039/d2cs00280a -
Organic & Biomolecular Chemistry Feb 2024The development of photodynamic therapy requires access to smart photosensitizers which combine appropriate photophysical and biological properties. Interestingly,...
The development of photodynamic therapy requires access to smart photosensitizers which combine appropriate photophysical and biological properties. Interestingly, supramolecular and dynamic covalent chemistries have recently shown their ability to produce novel architectures and responsive systems through simple self-assembly approaches. Herein, we report the straightforward formation of porphyrin-peptide conjugates and cage compounds which feature on their surface chemical groups promoting cell uptake and specific organelle targeting. We show that they self-assemble, in aqueous media, into positively-charged nanoparticles which generate singlet oxygen upon green light irradiation, while also undergoing a chemically-controlled disassembly due to the presence of reversible covalent linkages. Finally, the biological evaluation in cells revealed that they act as effective photosensitizers and promote synergistic effects in combination with Doxorubicin.
Topics: Porphyrins; Photosensitizing Agents; Photochemotherapy; Singlet Oxygen; Nanoparticles; Peptides
PubMed: 38289387
DOI: 10.1039/d3ob01887c -
Mini Reviews in Medicinal Chemistry 2021As a group of heterocyclic macrocycle organic natural compounds occurring universally in animal tissues and plants, porphyrins are composed of four modified pyrrole... (Review)
Review
As a group of heterocyclic macrocycle organic natural compounds occurring universally in animal tissues and plants, porphyrins are composed of four modified pyrrole subunits. Porphyrin analogues/ derivatives possess multiple biochemical properties because of their unique structures and have been extensively investigated in cancer treatment. Studies have shown that porphyrins and their derivatives have the ability to locate tumor cells in a variety of human cancers, and these compounds not only exhibit potent therapeutic effects as photodynamic agents but also show promising properties in medicinal imaging, such as MRI, photoacoustic imaging, fluorescence imaging, and PET/SPECT imaging. This paper reviews the recent reports of porphyrin derivatives as therapeutic agents used in tumor therapies, such as sonodynamic therapy, photodynamic therapy and radiotherapy, as well as the imaging agents for multimodality tumor imaging. The limitations of porphyrin-based compounds in tumor treatments and future prospects are also summarized.
Topics: Contrast Media; Humans; Magnetic Resonance Imaging; Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 33302834
DOI: 10.2174/1389557520999201209212745