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ACS Omega May 2024Modulation of intramolecular charge transfer (ICT) has been tested in two antimony(V) porphyrins, SbT(DMP)P(OMe)·PF and SbT(DMP)P(OTFE)·PF, where the -positions are...
Modulation of intramolecular charge transfer (ICT) has been tested in two antimony(V) porphyrins, SbT(DMP)P(OMe)·PF and SbT(DMP)P(OTFE)·PF, where the -positions are occupied by 3,5-dimethoxyphenyl (DMP), and the axial positions are linked with either methoxy (OMe) or trifluoroethoxy (OTFE) units, respectively. The presence of the Sb(+5) ion makes the porphyrin center electron poor. Under this situation, placing electron-rich units in the -position creates a condition for push-pull type ICT in the SbT(DMP)P(OMe)·PF. Remarkably, it is shown that the ICT character can be further enhanced in SbT(DMP)P(OTFE)·PF with the help of electron-withdrawing TFE units in the axial position, which makes the porphyrin center even more electron scarce. The steady-state and transient studies as well as solvatochromism studies establish the ICT in SbT(DMP)P(OMe)·PF and SbT(DMP)P(OTFE)·PF, and the strength of the ICT can be modulated by exploiting the structural properties of antimony(V) porphyrin. The existence of ICT is further supported by density functional theory calculations. The transient studies show that upon excitation of these porphyrin, their charge-transfer states convert to a full charger-separated states with appreciable lifetimes.
PubMed: 38826543
DOI: 10.1021/acsomega.4c01773 -
Ultrasonics Sonochemistry Jul 2024Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by infiltration of inflammatory cells, hyperplasia of synovium, and destruction of the...
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by infiltration of inflammatory cells, hyperplasia of synovium, and destruction of the joint cartilage. Owing to the low drug delivery efficiency and limited immunosuppression effect, complete cure for RA remains a formidable challenge. Here, we show that live macrophages (Mφs) carrying protoporphyrin-loaded FeO nanoparticles can migrate to the RA tissues and inhibit the inflammation by sonodynamic therapy. The inflammation of RA leads to the release of cytokines, which guides the migration of the Mφs into the RA tissues, realizing precise delivery of therapeutics. The following sonodynamic therapy induced by ultrasound and protoporphyrin destructs the proliferating synovial cells and also infiltrated inflammatory cells, demonstrating significant therapeutic effect for RA. Meanwhile, the cytokines and relapse of RA can be remarkably suppressed because of the efficient damage to the resident inflammatory cells.
Topics: Arthritis, Rheumatoid; Macrophages; Protoporphyrins; Animals; Ultrasonic Therapy; Mice; RAW 264.7 Cells; Magnetite Nanoparticles; Cytokines; Humans
PubMed: 38820932
DOI: 10.1016/j.ultsonch.2024.106928 -
Scientific Reports May 2024Atherosclerosis is the build-up of fatty plaques within blood vessel walls, which can occlude the vessels and cause strokes or heart attacks. It gives rise to both...
Atherosclerosis is the build-up of fatty plaques within blood vessel walls, which can occlude the vessels and cause strokes or heart attacks. It gives rise to both structural and biomolecular changes in the vessel walls. Current single-modality imaging techniques each measure one of these two aspects but fail to provide insight into the combined changes. To address this, our team has developed a dual-modality imaging system which combines optical coherence tomography (OCT) and fluorescence imaging that is optimized for a porphyrin lipid nanoparticle that emits fluorescence and targets atherosclerotic plaques. Atherosclerosis-prone apolipoprotein (Apo)e mice were fed a high cholesterol diet to promote plaque development in descending thoracic aortas. Following infusion of porphyrin lipid nanoparticles in atherosclerotic mice, the fiber-optic probe was inserted into the aorta for imaging, and we were able to robustly detect a porphyrin lipid-specific fluorescence signal that was not present in saline-infused control mice. We observed that the nanoparticle fluorescence colocalized in areas of CD68 macrophages. These results demonstrate that our system can detect the fluorescence from nanoparticles, providing complementary biological information to the structural information obtained from simultaneously acquired OCT.
Topics: Tomography, Optical Coherence; Animals; Plaque, Atherosclerotic; Nanoparticles; Mice; Porphyrins; Optical Imaging; Disease Models, Animal; Atherosclerosis; Macrophages; Lipoproteins, HDL
PubMed: 38811670
DOI: 10.1038/s41598-024-63132-6 -
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 2024malaria parasites invade and multiply inside red blood cells (RBCs), the most iron-rich compartment in humans. Like all cells, requires nutritional iron to support...
malaria parasites invade and multiply inside red blood cells (RBCs), the most iron-rich compartment in humans. Like all cells, 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 iron acquisition has not been tested. Our phylogenetic studies indicate that 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