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Life Science Alliance Aug 2024Cancer cells exhibit a metabolic phenotype termed “porphyrin overdrive,” characterized by dysregulated heme metabolic pathways for intermediate accumulation. This...
Cancer cells exhibit a metabolic phenotype termed “porphyrin overdrive,” characterized by dysregulated heme metabolic pathways for intermediate accumulation. This rewiring is cancer-essential and cancer-specific. Targeting this vulnerability with a “bait-and-kill” strategy shows promise in eradicating malignant cells.
PubMed: 38803226
DOI: 10.26508/lsa.202402816 -
International Journal of Nanomedicine 2024Medical imaging modalities, such as magnetic resonance imaging (MRI), ultrasound, and fluorescence imaging, have gained widespread acceptance in clinical practice for...
BACKGROUND
Medical imaging modalities, such as magnetic resonance imaging (MRI), ultrasound, and fluorescence imaging, have gained widespread acceptance in clinical practice for tumor diagnosis. Each imaging modality has its own unique principles, advantages, and limitations, thus necessitating a multimodal approach for a comprehensive disease understanding of the disease process. To enhance diagnostic precision, physicians frequently integrate data from multiple imaging modalities, driving research advancements in multimodal imaging technology research.
METHODS
In this study, hematoporphyrin-poly (lactic acid) (HP-PLLA) polymer was prepared via ring-opening polymerization and thoroughly characterized using FT-IR, H-NMR, XRD, and TGA. HP-PLLA based nanoparticles encapsulating perfluoropentane (PFP) and salicylic acid were prepared via emulsion-solvent evaporation. Zeta potential and mean diameter were assessed using DLS and TEM. Biocompatibility was evaluated via cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed with a dedicated apparatus, while CEST MRI was conducted using a 7.0 T animal scanner.
RESULTS
We designed and prepared a novel dual-mode nanoimaging probe SA/PFP@HP-PLLA NPs. PFP enhanced US imaging, while salicylic acid bolstered CEST imaging. With an average size of 74.43 ± 1.12 nm, a polydispersity index of 0.175 ± 0.015, and a surface zeta potential of -64.1 ± 2.11 mV. These NPs exhibit excellent biocompatibility and stability. Both in vitro and in vivo experiments confirmed the SA/PFP@HP-PLLA NP's ability to improve tumor characterization and diagnostic precision.
CONCLUSION
The SA/PFP@HP-PLLA NPs demonstrate promising dual-modality imaging capabilities, indicating their potential for preclinical and clinical use as a contrast agent.
Topics: Fluorocarbons; Magnetic Resonance Imaging; Animals; Polyesters; Nanoparticles; Humans; Salicylic Acid; Hematoporphyrins; Mice; Ultrasonography; Contrast Media; Cell Line, Tumor; Multimodal Imaging; Pentanes
PubMed: 38799695
DOI: 10.2147/IJN.S454486 -
ACS Omega May 2024Antibiotics are frequently used to treat, prevent, or control bacterial infections, but in recent years, infections resistant to all known classes of conventional...
Antibiotics are frequently used to treat, prevent, or control bacterial infections, but in recent years, infections resistant to all known classes of conventional antibiotics have significantly grown. The development of novel, nontoxic, and nonincursive antimicrobial methods that work more quickly and efficiently than the present antibiotics is required to combat this growing public health issue. Here, Co(II) and Zn(II) derivatives of tetrakis(1-methylpyridinium-4yl)porphyrin [HTMPyP] as a tetra(ρ-toluenesulfonate) were synthesized and purified to investigate their interactions with DNA (pH 7.40, 25 °C) using UV-vis, fluorescence techniques, and antimicrobial activity. UV-vis results showed that [HTMPyP] had a high hypochromicity (∼64%) and a substantial bathochromic shift (Δλ, 14 nm), while [Co(II)TMPyP] and [Zn(II)TMPyP] showed little hypochromicity (∼37%) and a small bathochromic shift (Δλ, 3-6 nm). Results reveal that [HTMPyP] interacts with DNA via intercalation, while Co(II)- and [Zn(II)TMPyP] interact with DNA via outside self-stacking. Fluorescence results also confirmed the interaction of [HTMPyP] and the metalloporphyrins with DNA. Results of the antimicrobial activity assay revealed that the metalloporphyrins showed inhibitory effects on Gram-positive and Gram-negative bacteria and fungi, but that neither the counterions nor [HTMPyP] exhibited any inhibitory effects. Mechanism of antimicrobial activities of metalloporphyrins are discussed.
PubMed: 38799349
DOI: 10.1021/acsomega.4c01708 -
Journal of Clinical Biochemistry and... May 2024Photodynamic therapy (PDT) is useful for various cancers such as high-grade glioma and cancers of other organs. However, the mechanism of tumor-specific accumulation of...
Photodynamic therapy (PDT) is useful for various cancers such as high-grade glioma and cancers of other organs. However, the mechanism of tumor-specific accumulation of porphyrin is not clear. The authors previously reported that heme carrier protein 1 (HCP1) contributes to the transport of porphyrins; specifically, we showed that the production of cancer-specific reactive oxygen species from mitochondria (mitROS) leads in turn to enhanced HCP1 expression. Indomethacin (IND), a non-steroidal anti-inflammatory drug, increases ROS production by affecting mitochondrial electron transfer system. In the present work, the authors investigated the effect of pretreatment with IND on cancer-specific porphyrin accumulation, using both a glioma cell line and a rat brain tumor model. This work demonstrated that exposure of a rat glioma cell to IND results in increased generation of cancer-specific mitROS and accumulation of HCP1 expression and porphyrin concentration. Additionally, systemic dosing of a brain tumor animal model with IND resulted in elevated cellular accumulation of porphyrin in tumor cell. This is an effect not seen with normal brain tissue. Thus, the administration of IND increases intracellular porphyrin concentrations in tumor cell without exerting harmful effects on normal brain tissue, and increased porphyrin concentration in tumor cell may lead to improved PDT effect.
PubMed: 38799142
DOI: 10.3164/jcbn.23-20 -
BioRxiv : the Preprint Server For... Jun 2024Plasmodium falciparum malaria parasites invade and multiply inside red blood cells (RBCs), the most iron-rich compartment in humans. Like all cells, P. falciparum...
Plasmodium falciparum malaria parasites invade and multiply inside red blood cells (RBCs), the most iron-rich compartment in humans. Like all cells, P. falciparum requires nutritional iron to support essential metabolic pathways, but the critical mechanisms of iron acquisition and trafficking during RBC infection have remained obscure. Parasites internalize and liberate massive amounts of heme during large-scale digestion of RBC hemoglobin within an acidic food vacuole (FV) but lack a heme oxygenase to release porphyrin-bound iron. Although most FV heme is sequestered into inert hemozoin crystals, prior studies indicate that trace heme escapes biomineralization and is susceptible to non-enzymatic degradation within the oxidizing FV environment to release labile iron. Parasites retain a homolog of divalent metal transporter 1 (DMT1), a known mammalian iron transporter, but its role in P. falciparum iron acquisition has not been tested. Our phylogenetic studies indicate that P. falciparum DMT1 (PfDMT1) retains conserved molecular features critical for metal transport. We localized this protein to the FV membrane and defined its orientation in an export-competent topology. Conditional knockdown of PfDMT1 expression is lethal to parasites, which display broad cellular defects in iron-dependent functions, including impaired apicoplast biogenesis and mitochondrial polarization. Parasites are selectively rescued from partial PfDMT1 knockdown by supplementation with exogenous iron, but not other metals. These results support a cellular paradigm whereby PfDMT1 is the molecular gatekeeper to essential iron acquisition by blood-stage malaria parasites and suggest that therapeutic targeting of PfDMT1 may be a potent antimalarial strategy.
PubMed: 38798484
DOI: 10.1101/2024.05.10.587216 -
Chemosphere Aug 2024Research has demonstrated the presence of viruses in wastewater (WW), which can remain viable for a long period, posing potential health risks. Conventional WW treatment...
Research has demonstrated the presence of viruses in wastewater (WW), which can remain viable for a long period, posing potential health risks. Conventional WW treatment methods involving UV light, chlorine and ozone efficiently reduce microbial concentrations, however, they produce hazardous byproducts and microbial resistance that are detrimental to human health and the ecosystem. Hence, there is a need for novel disinfection techniques. Antimicrobial Photodynamic Inactivation (PDI) emerges as a promising strategy, utilizing photosensitizers (PS), light, and dioxygen to inactivate viruses. This study aims to assess the efficacy of PDI by testing methylene blue (MB) and the cationic porphyrin TMPyP as PSs, along a low energy consuming white light source (LED) at an irradiance of 50 mW/cm, for the inactivation of bacteriophage Phi6. Phi6 serves as an enveloped RNA-viruses surrogate model in WW. PDI experiments were conducted in a buffer solution (PBS) and real WW matrices (filtered and non-filtered). Considering the environmental release of the treated effluents, this research also evaluated the ecotoxicity of the resulting solution (post-PDI treatment effluent) on the model organism Daphnia magna, following the Organisation for Economic Cooperation and Development (OECD) immobilization technical 202 guideline. Daphnids were exposed to WW containing the tested PS at different concentrations and dilutions (accounting for the dilution factor during WW release into receiving waters) over 48 h. The results indicate that PDI with MB efficiently inactivated the model virus in the different aqueous matrices, achieving reductions superior to 8 log PFU/mL, after treatments of 5 min in PBS and of ca. 90 min in WW. Daphnids survival increased when subjected to the PDI-treated WW with MB, considering the dilution factor. Overall, the effectiveness of PDI in eliminating viruses in WW, the fading of the toxic effects on daphnids after MB' irradiation and the rapid dilution effect upon WW release in the environment highlight the possibility of using MB in WW PDI-disinfection.
Topics: Wastewater; Disinfection; Daphnia; Photosensitizing Agents; Animals; Methylene Blue; Porphyrins; Bacteriophages; Waste Disposal, Fluid; Water Purification; Ecotoxicology
PubMed: 38797202
DOI: 10.1016/j.chemosphere.2024.142421 -
Biomedicine & Pharmacotherapy =... Jul 2024Antiviral medicines to treat COVID-19 are still scarce. Porphyrins and porphyrin derivatives (PDs) usually present broad-spectrum antiviral activity with low risk of...
Antiviral medicines to treat COVID-19 are still scarce. Porphyrins and porphyrin derivatives (PDs) usually present broad-spectrum antiviral activity with low risk of resistance development. In fact, some PDs are clinically approved to be used in anti-cancer photodynamic therapy and repurposing clinically approved PDs might be an alternative to treat COVID-19. Here, we characterize the ability of temoporfin, verteporfin, talaporfin and redaporfin to inactivate SARS-CoV-2 infectious particles. PDs light-dependent and -independent effect on SARS-CoV-2 infectivity were evaluated. PDs photoactivation successfully inactivated SARS-CoV-2 with very low concentrations and light dose. However, only temoporfin and verteporfin inactivated SARS-CoV-2 in the dark, being verteporfin the most effective. PDs treatment reduced viral load in infected Caco-2 cells, while not inducing cytotoxicity. Furthermore, light-independent treatment with temoporfin and verteporfin act on early stages of viral infection. Using lipid vehicles as membrane models, we characterized PDs interaction to the viral envelope. Verteporfin presented the lowest IC50 for viral inactivation and the highest partition coefficients (K) towards lipid bilayers. Curiously, although temoporfin and redaporfin presented similar Ks, redaporfin did not present light-independent antiviral activity, and only temoporfin and verteporfin caused lipid membrane disorder. In fact, redaporfin is located closer to the bilayer surface, while temoporfin and verteporfin are located closer to the centre. Our results suggest that viral envelope affinity, with penetration and destabilization of the lipid bilayer, seems critical to mediate PDs antiviral activity. Altogether, these findings open new avenues for the off-label application of temoporfin and verteporfin in the systemic treatment of COVID-19.
Topics: Humans; Porphyrins; SARS-CoV-2; Drug Repositioning; Antiviral Agents; Caco-2 Cells; COVID-19 Drug Treatment; Antineoplastic Agents; Viral Envelope; Animals; Chlorocebus aethiops; Vero Cells; COVID-19
PubMed: 38795638
DOI: 10.1016/j.biopha.2024.116768 -
Water Research Jul 2024Nano zero-valent metals (nZVMs) have been extensively utilized for decades in the reductive remediation of groundwater contaminated with chlorinated organic compounds,...
Nano zero-valent metals (nZVMs) have been extensively utilized for decades in the reductive remediation of groundwater contaminated with chlorinated organic compounds, owing to their robust reducing capabilities, simple application, and cost-effectiveness. Nevertheless, there remains a dearth of information regarding the efficient reductive defluorination of linear or branched per- and polyfluoroalkyl substances (PFASs) using nZVMs as reductants, largely due to the absence of appropriate catalysts. In this work, various soluble porphyrin ligands [[meso‑tetra(4-carboxyphenyl)porphyrinato]cobalt(III)]Cl·7HO (CoTCPP), [[meso‑tetra(4-sulfonatophenyl) porphyrinato]cobalt(III)]·9HO (CoTPPS), and [[meso‑tetra(4-N-methylpyridyl) porphyrinato]cobalt(II)](I)·4HO (CoTMpyP) have been explored for defluorination of PFASs in the presence of the nZn as reductant. Among these, the cationic CoTMpyP showed best defluorination efficiencies for br-perfluorooctane sulfonate (PFOS) (94%), br-perfluorooctanoic acid (PFOA) (89%), and 3,7-Perfluorodecanoic acid (PFDA) (60%) after 1 day at 70 °C. The defluorination rate constant of this system (CoTMpyP-nZn) is 88-164 times higher than the VB-nZn system for the investigated br-PFASs. The CoTMpyP-nZn also performed effectively at room temperature (55% for br-PFOS, 55% for br-PFOA and 25% for 3,7-PFDA after 1day), demonstrating the great potential of in-situ application. The effect of various solubilizing substituents, electron transfer flow and corresponding PFASs defluorination pathways in the CoTMpyP-nZn system were investigated by both experiments and density functional theory (DFT) calculations. SYNOPSIS: Due to the unavailability of active catalysts, available information on reductive remediation of PFAS by zero-valent metals (ZVMs) is still inadequate. This study explores the effective defluorination of various branched PFASs using soluble porphyrin-ZVM systems and offers a systematic approach for designing the next generation of catalysts for PFAS remediation.
Topics: Zinc; Porphyrins; Fluorocarbons; Metalloporphyrins; Water Pollutants, Chemical; Oxidation-Reduction
PubMed: 38795548
DOI: 10.1016/j.watres.2024.121803 -
Molecules (Basel, Switzerland) May 2024We present a Raman spectroscopy study of the vibrational properties of free-base meso-tetra(4-pyridyl) porphyrin polycrystals under various temperature and hydrostatic...
We present a Raman spectroscopy study of the vibrational properties of free-base meso-tetra(4-pyridyl) porphyrin polycrystals under various temperature and hydrostatic pressure conditions. The combination of experimental results and Density Functional Theory (DFT) calculations allows us to assign most of the observed Raman bands. The modifications in the Raman spectra when excited with 488 nm and 532 nm laser lights indicate that a resonance effect in the Qy band is taking place. The pressure-dependent results show that the resonance conditions change with increasing pressure, probably due to the shift of the electronic transitions. The temperature-dependent results show that the relative intensities of the Raman modes change at low temperatures, while no frequency shifts are observed. The experimental and theoretical analysis presented here suggest that these molecules are well represented by the C2v point symmetry group.
PubMed: 38792223
DOI: 10.3390/molecules29102362 -
Molecules (Basel, Switzerland) May 2024The impact of fluorine on plants remains poorly understood. We examined duckweed growth in extracts of soil contaminated with fluorine leached from chicken manure....
The impact of fluorine on plants remains poorly understood. We examined duckweed growth in extracts of soil contaminated with fluorine leached from chicken manure. Additionally, fluorine levels were analyzed in fresh manure, outdoor-stored manure, and soil samples at varying distances from the manure pile. Fresh manure contained 37-48 mg F × kg, while soil extracts contained 2.1 to 4.9 mg F × kg. We evaluated the physiological effects of fluorine on duckweed cultured on soil extracts or in 50% Murashige-Skoog (MS) medium supplemented with fluorine concentrations matching those in soil samples (2.1 to 4.9 mg F × L), as well as at 0, 4, and 210 mg × L. Duckweed exposed to fluorine displayed similar toxicity symptoms whether in soil extracts or supplemented medium. Fluoride at concentrations of 2.1 to 4.9 mg F × L reduced the intact chlorophyll content, binding the porphyrin ring at position 3 without affecting Mg. This reaction resulted in absorption peak shifted towards shorter wavelengths and formation of a new band of the F- complex at λ = 421 nm. Moreover, plants exposed to low concentrations of fluorine exhibited increased activities of aminolevulinic acid dehydratase and chlorophyllase, whereas the activities of both enzymes sharply declined when the fluoride concentration exceeded 4.9 mg × L. Consequently, fluorine damages , disrupts the activity of chlorophyll-metabolizing enzymes, and diminishes the plant growth rate, even when the effects of these disruptions are too subtle to be discerned by the naked human eye.
Topics: Araceae; Chlorophyll; Fluorides; Soil Pollutants; Soil; Manure; Environmental Pollution
PubMed: 38792197
DOI: 10.3390/molecules29102336