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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 -
International Journal of Molecular... May 2022Oxygen evolution reaction (OER) plays a pivotal role in the development of renewable energy methods, such as water-splitting devices and the use of Zn-air batteries.... (Review)
Review
Oxygen evolution reaction (OER) plays a pivotal role in the development of renewable energy methods, such as water-splitting devices and the use of Zn-air batteries. First-row transition metal complexes are promising catalyst candidates due to their excellent electrocatalytic performance, rich abundance, and cheap price. Metalloporphyrins are a class of representative high-efficiency complex catalysts owing to their structural and functional characteristics. However, OER based on porphyrin systems previously have been paid little attention in comparison to the well-described oxygen reduction reaction (ORR), hydrogen evolution reaction, and CO reduction reaction. Recently, porphyrin-based systems, including both small molecules and porous polymers for electrochemical OER, are emerging. Accordingly, this review summarizes the recent advances of porphyrin-based systems for electrochemical OER. Firstly, the electrochemical OER for water oxidation is discussed, which shows various methodologies to achieve catalysis from homogeneous to heterogeneous processes. Subsequently, the porphyrin-based catalytic systems for bifunctional oxygen electrocatalysis including both OER and ORR are demonstrated. Finally, the future development of porphyrin-based catalytic systems for electrochemical OER is briefly prospected.
Topics: Catalysis; Oxidation-Reduction; Oxygen; Porphyrins; Water
PubMed: 35682721
DOI: 10.3390/ijms23116036 -
Sensors (Basel, Switzerland) Aug 2021The advanced and widespread use of microfluidic devices, which are usually fabricated in polydimethylsiloxane (PDMS), requires the integration of many sensors, always...
The advanced and widespread use of microfluidic devices, which are usually fabricated in polydimethylsiloxane (PDMS), requires the integration of many sensors, always compatible with microfluidic fabrication processes. Moreover, current limitations of the existing optical and electrochemical oxygen sensors regarding long-term stability due to sensor degradation, biofouling, fabrication processes and cost have led to the development of new approaches. Thus, this manuscript reports the development, fabrication and characterization of a low-cost and highly sensitive dissolved oxygen optical sensor based on a membrane of PDMS doped with platinum octaethylporphyrin (PtOEP) film, fabricated using standard microfluidic materials and processes. The excellent mechanical and chemical properties (high permeability to oxygen, anti-biofouling characteristics) of PDMS result in membranes with superior sensitivity compared with other matrix materials. The wide use of PtOEP in sensing applications, due to its advantage of being easily synthesized using microtechnologies, its strong phosphorescence at room temperature with a quantum yield close to 50%, its excellent Strokes Shift as well as its relatively long lifetime (75 µs), provide the suitable conditions for the development of a miniaturized luminescence optical oxygen sensor allowing long-term applications. The influence of the PDMS film thickness (0.1-2.5 mm) and the PtOEP concentration (363, 545, 727 ppm) in luminescent properties are presented. This enables to achieve low detection levels in a gas media range from 0.5% up to 20%, and in liquid media from 0.5 mg/L up to 3.3 mg/L at 1 atm, 25 °C. As a result, we propose a simple and cost-effective system based on a LED membrane photodiode system to detect low oxygen concentrations for in situ applications.
Topics: Dimethylpolysiloxanes; Oxygen; Platinum; Porphyrins
PubMed: 34451087
DOI: 10.3390/s21165645 -
Chemical Society Reviews Aug 2019Bioinspired nanostructures can be the ideal functional smart materials to bridge the fundamental biology, biomedicine and nanobiotechnology fields. Among them, short... (Review)
Review
Bioinspired nanostructures can be the ideal functional smart materials to bridge the fundamental biology, biomedicine and nanobiotechnology fields. Among them, short peptides are among the most preferred building blocks as they can self-assemble to form versatile supramolecular architectures displaying unique physical and chemical properties, including intriguing optical features. Herein, we discuss the progress made over the past few decades in the design and characterization of optical short peptide nanomaterials, focusing on their intrinsic photoluminescent and waveguiding performances, along with the diverse modulation strategies. We review the complicated optical properties and the advanced applications of photoactive short peptide self-assemblies, including photocatalysis, as well as photothermal and photodynamic therapy. The diverse advantages of photoactive short peptide self-assemblies, such as eco-friendliness, morphological and functional flexibility, and ease of preparation and modification, endow them with the capability to potentially serve as next-generation, bio-organic optical materials, allowing the bridging of the optics world and the nanobiotechnology field.
Topics: Catalysis; Glucose; Humans; Hydrogels; Light; Nanostructures; Neoplasms; Peptides; Photochemotherapy; Porphyrins
PubMed: 31237282
DOI: 10.1039/c9cs00085b -
Molecules (Basel, Switzerland) Aug 2023Tolyporphins were discovered some 30 years ago as part of a global search for antineoplastic compounds from cyanobacteria. To date, the culture HT-58-2, comprised of a... (Review)
Review
Tolyporphins were discovered some 30 years ago as part of a global search for antineoplastic compounds from cyanobacteria. To date, the culture HT-58-2, comprised of a cyanobacterium-microbial consortium, is the sole known producer of tolyporphins. Eighteen tolyporphins are now known-each is a free base tetrapyrrole macrocycle with a dioxobacteriochlorin (14), oxochlorin (3), or porphyrin (1) chromophore. Each compound displays two, three, or four open β-pyrrole positions and two, one, or zero appended -glycoside (or -OH or -OAc) groups, respectively; the appended groups form part of a geminal disubstitution motif flanking the oxo moiety in the pyrroline ring. The distinct structures and repertoire of tolyporphins stand alone in the large pigments-of-life family. Efforts to understand the cyanobacterial origin, biosynthetic pathways, structural diversity, physiological roles, and potential pharmacological properties of tolyporphins have attracted a broad spectrum of researchers from diverse scientific areas. The identification of putative biosynthetic gene clusters in the HT-58-2 cyanobacterial genome and accompanying studies suggest a new biosynthetic paradigm in the tetrapyrrole arena. The present review provides a comprehensive treatment of the rich science concerning tolyporphins.
Topics: Tetrapyrroles; Cyanobacteria; Porphyrins; Cardiac Glycosides
PubMed: 37630384
DOI: 10.3390/molecules28166132 -
Molecules (Basel, Switzerland) May 2022Porphyrin ligands, showing a significant affinity for cancer cells, also have the ability to chelate metallic radioisotopes to form potential diagnostic... (Review)
Review
Porphyrin ligands, showing a significant affinity for cancer cells, also have the ability to chelate metallic radioisotopes to form potential diagnostic radiopharmaceuticals. They can be applied in single-photon emission computed tomography (SPECT) and positron emission tomography (PET) to evaluate metabolic changes in the human body for tumor diagnostics. The aim of this paper is to present a short overview of the main metallic radionuclides complexed by porphyrin ligands and used in these techniques. These chelation reactions are discussed in terms of the complexation conditions and kinetics and the complex stability.
Topics: Chelating Agents; Humans; Ligands; Molecular Imaging; Nuclear Medicine; Porphyrins; Radioisotopes
PubMed: 35630788
DOI: 10.3390/molecules27103311 -
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 -
Molecules (Basel, Switzerland) Jul 2019Antibiotics are commonly used to control, treat, or prevent bacterial infections, however bacterial resistance to all known classes of traditional antibiotics has... (Review)
Review
Antibiotics are commonly used to control, treat, or prevent bacterial infections, however bacterial resistance to all known classes of traditional antibiotics has greatly increased in the past years especially in hospitals rendering certain therapies ineffective. To limit this emerging public health problem, there is a need to develop non-incursive, non-toxic, and new antimicrobial techniques that act more effectively and quicker than the current antibiotics. One of these effective techniques is antibacterial photodynamic therapy (aPDT). This review focuses on the application of porphyrins in the photo-inactivation of bacteria. Mechanisms of bacterial resistance and some of the current 'greener' methods of synthesis of meso-phenyl porphyrins are discussed. In addition, significance and limitations of aPDT are also discussed. Furthermore, we also elaborate on the current clinical applications and the future perspectives and directions of this non-antibiotic therapeutic strategy in combating infectious diseases.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Humans; Light; Photochemotherapy; Porphyrins
PubMed: 31277423
DOI: 10.3390/molecules24132456 -
Molecules (Basel, Switzerland) Apr 2020Porphyrins and analogous macrocycles exhibit interesting photochemical, catalytic, and luminescence properties demonstrating high potential in the treatment of several... (Review)
Review
Porphyrins and analogous macrocycles exhibit interesting photochemical, catalytic, and luminescence properties demonstrating high potential in the treatment of several diseases. Among them can be highlighted the possibility of application in photodynamic therapy and antimicrobial/antiparasitic PDT, for example, of malaria parasite. However, the low efficiency generally associated with their low solubility in water and bioavailability have precluded biomedical applications. Nanotechnology can provide efficient strategies to enhance bioavailability and incorporate targeted delivery properties to conventional pharmaceuticals, enhancing the effectiveness and reducing the toxicity, thus improving the adhesion to the treatment. In this way, those limitations can be overcome by using two main strategies: (1) Incorporation of hydrophilic substituents into the macrocycle ring while controlling the interaction with biological systems and (2) by including them in nanocarriers and delivery nanosystems. This review will focus on antiparasitic drugs based on porphyrin derivatives developed according to these two strategies, considering their vast and increasing applications befitting the multiple roles of these compounds in nature.
Topics: Antiparasitic Agents; Biosensing Techniques; Drug Compounding; Humans; Indoles; Isoindoles; Molecular Structure; Porphyrins; Structure-Activity Relationship
PubMed: 32365664
DOI: 10.3390/molecules25092080 -
Genes Nov 2020G-quadruplex (G4) is the non-canonical secondary structure of DNA and RNA formed by guanine-rich sequences. G4-forming sequences are abundantly located in telomeric... (Review)
Review
G-quadruplex (G4) is the non-canonical secondary structure of DNA and RNA formed by guanine-rich sequences. G4-forming sequences are abundantly located in telomeric regions and in the promoter and untranslated regions (UTR) of cancer-related genes, such as and . Extensive research has suggested that G4 is a potential molecular target for cancer therapy. Here, we reviewed G4 ligands as photosensitizers for cancer photodynamic therapy (PDT), which is a minimally invasive therapeutic approach. The photosensitizers, such as porphyrins, were found to be highly toxic against cancer cells via the generation of reactive oxidative species (ROS) upon photo-irradiation. Several porphyrin derivatives and analogs, such as phthalocyanines, which can generate ROS upon photo-irradiation, have been reported to act as G4 ligands. Therefore, they have been implicated as promising photosensitizers that can selectively break down cancer-related DNA and RNA forming G4. In this review, we majorly focused on the potential application of G4 ligands as photosensitizers, which would provide a novel strategy for PDT, especially molecularly targeted PDT (mtPDT).
Topics: Animals; G-Quadruplexes; Humans; Indoles; Isoindoles; Ligands; Molecular Targeted Therapy; Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins; Telomere
PubMed: 33198362
DOI: 10.3390/genes11111340