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1.
Lasers Med Sci ; 39(1): 151, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38839711

ABSTRACT

The aim of this study was to compare two types of light irradiation devices for antimicrobial photodynamic therapy (aPDT). A 660-nm light-emitting diode (LED) and a 665-nm laser diode (LD) were used for light irradiation, and 0.1 mg/L TONS 504, a cationic chlorin derivative, was used as the photosensitizer. We evaluated the light attenuation along the vertical and horizontal directions, temperature rise following light irradiation, and aPDT efficacy against Staphylococcus aureus under different conditions: TONS 504 only, light irradiation only, and TONS 504 with either LED (30 J/cm2) or LD light irradiation (continuous: 30 J/cm2; pulsed: 20 J/cm2 at 2/3 duty cycle, 10 J/cm2 at 1/3 duty cycle). Both LED and LD light intensities were inversely proportional to the square of the vertical distance from the irradiated area. Along the horizontal distance from the nadir of the light source, the LED light intensity attenuated according to the cosine quadrature law, while the LD light intensity did not attenuate within the measurable range. Following light irradiation, the temperature rise increased as the TONS 504 concentration increased in the order of pulsed LD < continuous LD < LED irradiation. aPDT with light irradiation only or TONS 504 only had no antimicrobial effect, while aPDT with TONS 504 under continuous or pulsed LD light irradiation provided approximately 3 log reduction at 30 J/cm2 and 20 J/cm2 and approximately 2 log reduction at 10 J/cm2. TONS 504-aPDT under pulsed LD light irradiation provided anti-microbial effect without significant temperature rise.


Subject(s)
Photochemotherapy , Photosensitizing Agents , Staphylococcus aureus , Photochemotherapy/methods , Staphylococcus aureus/drug effects , Staphylococcus aureus/radiation effects , Photosensitizing Agents/pharmacology , Humans , Lasers, Semiconductor/therapeutic use , Porphyrins/pharmacology , Temperature
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 319: 124529, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38824758

ABSTRACT

Considering the increasing number of pathogens resistant to commonly used antibiotics as well as antiseptics, there is an urgent need for antimicrobial approaches that can effectively inactivate pathogens without the risk of establishing resistance. An alternative approach in this context is antibacterial photodynamic therapy (APDT). APDT is a process that involves bacterial cell death using appropriate wavelength light energy and photosensitizer and causes the production of reactive oxygen species inside or outside the microbial cell depending on the penetration of light energy. In our study, a new porphyrin compound 4,4'-methylenebis(2-((E)-((4-(10,15,20-triphenylporphyrin-5-yl)phenyl)imino)methyl)phenol) (SP) was designed and synthesized as photosensitizer and its structure was clarified by NMR (13C and 1H) and mass determination method. Photophysical and photochemical properties were examined in detail using different methods. Singlet oxygen quantum yields were obtained as 0.48 and 0.59 by direct and indirect methods, respectively. Antibacterial activity studies have been conducted within the scope of biological activity and promising results have been obtained under LED light (500-700 nm, 265 V, 1500 LM), contributing to the antibacterial photodynamic therapy literature.


Subject(s)
Anti-Bacterial Agents , Photochemotherapy , Photosensitizing Agents , Porphyrins , Singlet Oxygen , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/chemical synthesis , Porphyrins/chemistry , Porphyrins/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Singlet Oxygen/metabolism , Singlet Oxygen/chemistry , Microbial Sensitivity Tests , Light , Bacteria/drug effects , Drug Design
3.
Int J Biol Macromol ; 272(Pt 1): 132893, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38838883

ABSTRACT

Foodborne pathogens result in a great harm to human, which is an urgent problem to be addressed. Herein, a novel cellulose-based packaging films with excellent anti-bacterial properties under visible light were prepared. A porphyrin-based covalent organic polymer (Por-COPs) was constructed, then covalently grafted onto dialdehyde cellulose (DAC). The addition of Por-COPs enhanced the mechanical, hydrophobicity, and water resistance of the DAC-based composite films. DAC/Por-COP-2.5 film exhibited outstanding properties for the photodynamic inactivation of bacteria under visible light irradiation, delivering inactivation efficiencies of 99.90 % and 99.45 % towards Staphylococcus aureus and Escherichia coli within 20 min. The DAC/Por-COPs films efficiently generated •O2- and 1O2 under visible light, thereby causing oxidative stress to cell membranes for bacterial inactivation. The prepared composite film forms a protective barrier against bacterial contamination. Results guide the development of high performance and more sustainable packaging films for the food sector.


Subject(s)
Cellulose , Escherichia coli , Porphyrins , Staphylococcus aureus , Cellulose/chemistry , Cellulose/analogs & derivatives , Cellulose/pharmacology , Porphyrins/chemistry , Porphyrins/pharmacology , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Light , Food Packaging/methods , Polymers/chemistry , Polymers/pharmacology , Sterilization/methods , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology
4.
Mikrochim Acta ; 191(7): 364, 2024 06 03.
Article in English | MEDLINE | ID: mdl-38831034

ABSTRACT

CdIn2S4 and zinc tetrakis(4-carboxyphenyl)porphyrin (ZnTCPP) were synthesized by hydrothermal method, and an organic dye-sensitized inorganic semiconductor ZnTCPP/CdIn2S4 type II heterojunction was constructed on a fluorine-doped tin oxide (FTO) substrate electrode. A sandwich immunostructure for signal-attenuation photoelectrochemical (PEC) detection of cardiac troponin I (cTnI) was constructed using the ZnTCPP/CdIn2S4/FTO photoanode and a horseradish peroxidase (HRP)-ZnFe2O4-Ab2-bovine serum albumin (BSA) immunolabeling complex. The bioenzyme HRP and the HRP-like nanozyme ZnFe2O4 can co-catalyze the oxidation of 4-chloro-1-naphthol (4-CN) by H2O2 to produce an insoluble precipitate on the photoanode, thus notably reducing the anodic photocurrent for quantitative determination of cTnI. Under the optimal conditions, the photocurrent at 0 V vs. SCE in 0.1 M phosphate buffer solution (pH 7.40) containing 0.1 M ascorbic acid was linear with the logarithm of cTnI concentration from 500 fg mL-1 to 50.0 ng mL-1, and the limit of detection (LOD, S/N = 3) is 0.15 pg mL-1. Spiked recoveries were 95.1% ~ 104% for assay of cTnI in human serum samples.


Subject(s)
Electrochemical Techniques , Limit of Detection , Tin Compounds , Troponin I , Troponin I/blood , Humans , Electrochemical Techniques/methods , Immunoassay/methods , Tin Compounds/chemistry , Catalysis , Horseradish Peroxidase/chemistry , Naphthols/chemistry , Metalloporphyrins/chemistry , Electrodes , Hydrogen Peroxide/chemistry , Serum Albumin, Bovine/chemistry , Photochemical Processes , Animals , Biosensing Techniques/methods , Semiconductors , Cattle , Sulfides/chemistry , Porphyrins/chemistry
5.
Biomater Sci ; 12(11): 2766-2785, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38717456

ABSTRACT

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.


Subject(s)
Metal-Organic Frameworks , Porphyrins , Porphyrins/chemistry , Porphyrins/chemical synthesis , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/chemical synthesis , Humans , Porosity , Animals
6.
Acta Biomater ; 181: 176-187, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38719158

ABSTRACT

Bacterial infections are among the most critical global health challenges that seriously threaten the security of human. To address this issue, a biocompatible engineered living hydrogel patch was developed by co-embedding engineered photothermal bacteria (EM), photosensitizer (porphyrin) and reactive oxygen species amplifier (laccase) in a protein hydrogel. Remarkably, the genetice engineered bacteria can express melanin granules in vivo and this allows them to exhibit photothermal response upon being exposed to NIR-II laser (1064 nm) irradiation. Besides, electrostatically adhered tetramethylpyridinium porphyrin (TMPyP) on the bacterial surface and encapsulated laccase (Lac) in protein gel can generate highly toxic singlet oxygen (1O2) and hydroxyl radical (·OH) in the presence of visible light and lignin, respectively. Interestingly, the engineered bacteria hydrogel patch (EMTL@Gel) was successfully applied in synergistic photothermal, photodynamic and chemodynamic therapy, in which it was able to efficiently treat bacterial infection in mouse wounds and enhance wound healing. This work demonstrates the concept of "fighting bacteria with bacteria" combining bacterial engineering and material engineering into an engineered living hydrogel path that can synergistically boost the therapeutic outcome. STATEMENT OF SIGNIFICANCE: Genetically engineered bacteria produce melanin granules in vivo, exhibiting remarkable photothermal properties. These bacteria, along with a photosensitizer (TMPyP) and a reactive oxygen species amplifier (laccase), are incorporated into a biocompatible protein hydrogel patch. Under visible light, the patch generates toxic singlet oxygen (1O2) and hydroxyl radical (·OH), demonstrates outstanding synergistic effects in photothermal, photodynamic, and chemodynamic therapy, effectively treating bacterial infections and promoting wound healing in mice.


Subject(s)
Hydrogels , Wound Healing , Wound Healing/drug effects , Animals , Hydrogels/chemistry , Hydrogels/pharmacology , Mice , Bacterial Infections/drug therapy , Biocompatible Materials/pharmacology , Biocompatible Materials/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Laccase/chemistry , Porphyrins/chemistry , Porphyrins/pharmacology , Escherichia coli/drug effects
7.
Colloids Surf B Biointerfaces ; 239: 113965, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38772084

ABSTRACT

Photodynamic therapy (PDT) has become a promising approach and non-invasive modality for cancer treatment, however the therapeutic effect of PDT is limited in tumor metastasis and local recurrence. Herein, a tumor targeted nanomedicine (designated as PCN@HA) is constructed for enhanced PDT against tumors. By modified with hyaluronic acid (HA), which could target the CD44 receptor that expressed on the cancer cells, the targeting ability of PCN@HA has been enhanced. Under light irradiation, PCN@HA can produce cytotoxic singlet oxygen (1O2) and kill cancer cells, then eliminate tumors. Furthermore, PCN@HA exhibits fluorescence (FL)/ photoacoustic (PA) effects for multimodal imaging-guided cancer treatment. And PCN@HA-mediated PDT also can induce immunogenic cell death (ICD) and stimulate adaptive immune responses by releasing of tumor antigens. By combining with anti-PD-L1 checkpoint blockade therapy, it can not only effectively suppress the growth of primary tumor, but also inhibit the metastatic tumor growth.


Subject(s)
Hyaluronic Acid , Immunotherapy , Metal-Organic Frameworks , Photochemotherapy , Porphyrins , Photochemotherapy/methods , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Immunotherapy/methods , Porphyrins/chemistry , Porphyrins/pharmacology , Animals , Humans , Mice , Hyaluronic Acid/chemistry , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/chemistry , Mice, Inbred BALB C , Singlet Oxygen/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Particle Size , Neoplasms/therapy , Neoplasms/immunology , Neoplasms/drug therapy , Neoplasms/pathology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry
8.
J Am Chem Soc ; 146(23): 15955-15964, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38814055

ABSTRACT

Artificial syntheses of biologically active molecules have been fruitful in many bioinspired catalysis applications. Specifically, verdoheme and biliverdin, bearing polypyrrole frameworks, have inspired catalyst designs to address energy and environmental challenges. Despite remarkable progress in benchtop synthesis of verdoheme and biliverdin derivatives, all reported syntheses, starting from metalloporphyrins or inaccessible biliverdin precursors, require multiple steps to achieve the final desired products. Additionally, such synthetic procedures use multiple reactants/redox agents and involve multistep purification/extraction processes that often lower the yield. However, in a single step using atmospheric oxygen, heme oxygenases selectively generate verdoheme or biliverdin from heme. Motivated by such enzymatic pathways, we report a single-step electrosynthesis of verdoheme or biliverdin derivatives from their corresponding meso-aryl-substituted metalloporphyrin precursors. Our electrosynthetic methods have produced a copper-coordinating verdoheme analog in >80% yield at an applied potential of 0.65 V vs ferrocene/ferrocenium in air-exposed acetonitrile solution with a suitable electrolyte. These electrosynthetic routes reached a maximum product yield within 8 h of electrolysis at room temperature. The major products of verdoheme and biliverdin derivatives were isolated, purified, and characterized using electrospray mass spectrometry, absorption spectroscopy, cyclic voltammetry, and nuclear magnetic resonance spectroscopy techniques. Furthermore, X-ray crystallographic data were collected for select cobalt (Co)- and Cu-chelating verdoheme and metal-free biliverdin products. Electrosynthesis routes for the selective modification at the macrocycle ring in a single step are not known yet, and therefore, we believe that this report would advance the scopes of electrosynthesis strategies.


Subject(s)
Biliverdine , Biliverdine/chemistry , Biliverdine/metabolism , Biliverdine/analogs & derivatives , Heme/chemistry , Heme/analogs & derivatives , Electrochemical Techniques , Heme Oxygenase (Decyclizing)/metabolism , Heme Oxygenase (Decyclizing)/chemistry , Porphyrins/chemistry , Molecular Structure
9.
Mikrochim Acta ; 191(6): 304, 2024 05 06.
Article in English | MEDLINE | ID: mdl-38710810

ABSTRACT

Dual-emissive fluorescence probes were designed by integrating porphyrin into the frameworks of UiO-66 for ratiometric fluorescence sensing of amoxicillin (AMX). Porphyrin integrated UiO-66 showed dual emission in the blue and red region. AMX resulted in the quenching of blue fluorescence component, attributable to the charge neutralization and hydrogen bonds induced energy transfer. AMX was detected using (F438/F654) as output signals. Two linear relationships were observed (from 10 to 1000 nM and 1 to 100 µM), with a limit of detection of 27 nM. The porphyrin integrated UiO-66 probe was used to detect AMX in practical samples. This work widens the road for the development of dual/multiple emissive fluorescence sensors for analytical applications, providing materials and theoretical supporting for food, environmental, and human safety.


Subject(s)
Amoxicillin , Anti-Bacterial Agents , Fluorescent Dyes , Milk , Porphyrins , Spectrometry, Fluorescence , Milk/chemistry , Porphyrins/chemistry , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/chemistry , Amoxicillin/analysis , Amoxicillin/chemistry , Fluorescent Dyes/chemistry , Animals , Spectrometry, Fluorescence/methods , Limit of Detection , Metal-Organic Frameworks/chemistry , Drug Residues/analysis , Food Contamination/analysis
10.
Biomacromolecules ; 25(6): 3671-3684, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38720431

ABSTRACT

Reactive oxygen species (ROS) have emerged as a promising treatment option for antibacterial and biofilm eradication. However, their therapeutic efficacy is significantly hampered by the unique microenvironments of diabetic wounds. In this study, we designed and synthesized porphyrin-based Fe covalent organic frameworks (Fe-COF) through a Schiff base condensation reaction. Subsequently, Fe-COF were encapsulated with hyaluronic acid (HA) through electrostatic adsorption, resulting in a novel formulation named HA-Fe-COF for diabetic wound healing. HA-Fe-COF were engineered to respond to hyaluronidase in the infected wound, leading to the controlled release of Fe-COF. Those released Fe-COF served a dual role as photosensitizers, generating singlet oxygen and localized heating when exposed to dual light sources. Additionally, they acted as peroxidase-like nanozymes, facilitating the production of ROS through enzymatic reactions. This innovative approach enabled a synergistic therapeutic effect combining photodynamic, photothermal, and chemodynamic modalities. Furthermore, the sustained release of HA from HA-Fe-COF promoted angiogenesis, collagen deposition, and re-epithelialization during the diabetic wound healing process. This "all-in-one" strategy offers a novel approach for the development of antimicrobial and biofilm eradication strategies that minimize damage to healthy tissues in vivo.


Subject(s)
Hyaluronic Acid , Metal-Organic Frameworks , Porphyrins , Wound Healing , Wound Healing/drug effects , Animals , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Porphyrins/chemistry , Porphyrins/pharmacology , Mice , Reactive Oxygen Species/metabolism , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/administration & dosage , Skin/drug effects , Humans , Wound Infection/drug therapy , Wound Infection/microbiology , Iron/chemistry , Photochemotherapy/methods , Hyaluronoglucosaminidase
11.
J Control Release ; 370: 438-452, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38701885

ABSTRACT

Triggering pyroptosis is a major new weathervane for activating tumor immune response. However, biodegradable pyroptosis inducers for the safe and efficient treatment of tumors are still scarce. Herein, a novel tumor microenvironment (TME)-responsive activation nanoneedle for pyroptosis induction, copper-tannic acid (CuTA), was synthesized and combined with the sonosensitizer Chlorin e6 (Ce6) to form a pyroptosis amplifier (CuTA-Ce6) for dual activation and amplification of pyroptosis by exogenous ultrasound (US) and TME. It was demonstrated that Ce6-triggered sonodynamic therapy (SDT) further enhanced the cellular pyroptosis caused by CuTA, activating the body to develop a powerful anti-tumor immune response. Concretely, CuTA nanoneedles with quadruple mimetic enzyme activity could be activated to an "active" state in the TME, destroying the antioxidant defense system of the tumor cells through self-destructive degradation, breaking the "immunosilent" TME, and thus realizing the pyroptosis-mediated immunotherapy with fewer systemic side effects. Considering the outstanding oxygen-producing capacity of CuTA and the distinctive advantages of US, the sonosensitizer Ce6 was attached to CuTA via an amide reaction, which further amplified the pyroptosis and sensitized pyroptosis-induced immunotherapy with the two-pronged strategy of CuTA enzyme-catalyzed cascade and US-driven SDT pathway to generate a "reactive oxygen species (ROS) storm". Conclusively, this work provided a representative paradigm for achieving safe, reliable and efficient pyroptosis, which was further enhanced by SDT for more robust immunotherapy.


Subject(s)
Chlorophyllides , Copper , Immunotherapy , Mice, Inbred BALB C , Porphyrins , Pyroptosis , Reactive Oxygen Species , Tumor Microenvironment , Pyroptosis/drug effects , Reactive Oxygen Species/metabolism , Porphyrins/administration & dosage , Immunotherapy/methods , Animals , Copper/administration & dosage , Cell Line, Tumor , Humans , Female , Ultrasonic Therapy/methods , Neoplasms/therapy , Neoplasms/immunology , Neoplasms/drug therapy , Mice
12.
Anal Chem ; 96(23): 9503-9511, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38780632

ABSTRACT

In this work, a micron-sized flower-like metal-organic frameworks (MOFs)-based boronate-affinity sandwich-type immunoassay was fabricated for the dual-mode glycoprotein assay. For proof of concept, the flower-like MOFs were synthesized from transition Cu nodes and tetrakis (4-carboxyphenyl) porphyrin (TCPP) ligands by spontaneous standing assembly. In addition, the specificity toward glycoprotein involved the antigen recognition as well as covalent bonding via the boronate-glycan affinity, and the immediate signal responses were initiated by textural decomposition of the flower-like MOFs. Intriguingly, Cu nodes, of which the valence state is dominant by CuI species, can endow the Fenton-like catalytic reaction of the fluorogenic substrate for generating fluorescence signals. For benefits, TCPP ligands, in which each TCPP molecule has four guest donors, can provide multiple valences for the assembly of cyclodextrin-capped gold nanoparticles via host-guest interaction for colorimetry output. Albeit important, the scaling micrometer patterns for the flower-like MOFs carrying numerous Cu nodes and TCPP ligands can also function as amplifying units, signifying the output signal. The detection limit of the dual-mode glycoprotein assay can reach 10.5 nM for the fluorescence mode and 18.7 nM for the colorimetry mode, respectively. Furthermore, the merits of harvesting different signal generators toward the multimodal readout patterns can allow the mutual verification and make the analytical results more reliable. Collectively, our proposed assay may offer a new idea in combining the inherent textural merits from MOFs for dual signal generators, which can also emphasize accurate detection capability for glycoprotein assay.


Subject(s)
Glycoproteins , Metal-Organic Frameworks , Metal-Organic Frameworks/chemistry , Glycoproteins/analysis , Glycoproteins/chemistry , Copper/chemistry , Porphyrins/chemistry , Immunoassay/methods , Gold/chemistry , Metal Nanoparticles/chemistry , Humans , Boronic Acids/chemistry , Limit of Detection , Particle Size
13.
Water Res ; 258: 121803, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38795548

ABSTRACT

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 [[meso­tetra(4-carboxyphenyl)porphyrinato]cobalt(III)]Cl·7H2O (CoTCPP), [[meso­tetra(4-sulfonatophenyl) porphyrinato]cobalt(III)]·9H2O (CoTPPS), and [[meso­tetra(4-N-methylpyridyl) porphyrinato]cobalt(II)](I)4·4H2O (CoTMpyP) have been explored for defluorination of PFASs in the presence of the nZn0 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-nZn0) is 88-164 times higher than the VB12-nZn0 system for the investigated br-PFASs. The CoTMpyP-nZn0 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-nZn0 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.


Subject(s)
Zinc , Zinc/chemistry , Porphyrins/chemistry , Fluorocarbons/chemistry , Metalloporphyrins/chemistry , Water Pollutants, Chemical/chemistry , Oxidation-Reduction
14.
Photochem Photobiol Sci ; 23(6): 1195-1208, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38703274

ABSTRACT

The effect of photodynamic inactivation (PDI) sensitized by 5,10,15,20-tetra(4-N,N,N-trimethylammoniophenyl)porphyrin (TMAP4+) on different components of mono- and dual-species biofilms of Staphylococcus aureus and Escherichia coli was determined by different methods. First, the plate count technique showed that TMAP4+-PDI was more effective on S. aureus than E. coli biofilm. However, crystal violet staining revealed no significant differences between before and after PDI biofilms of both bacteria. On the other hand, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method indicated a reduction in viable cells as the light exposure time increases in both, mono- and dual-species biofilms. Furthermore, it was determined that as the irradiation time increases, the amount of extracellular polymeric substances present in the biofilms decreased. This effect was presented in both strains and in the mixed biofilm, being more evident in S. aureus mono-specie biofilm. Finally, scanning electron microscopy analysis showed a decrease in the number of cells forming the biofilm after photosensitization treatments. This information makes it possible to determine whether the photodynamic action is based on damage to metabolic activity, extracellular matrix and/or biomass, which may be useful in establishing a fully effective PDI protocol for the treatment of microorganisms growing as biofilms.


Subject(s)
Biofilms , Escherichia coli , Photosensitizing Agents , Staphylococcus aureus , Biofilms/drug effects , Staphylococcus aureus/drug effects , Staphylococcus aureus/physiology , Escherichia coli/drug effects , Escherichia coli/physiology , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Porphyrins/pharmacology , Porphyrins/chemistry , Light , Microscopy, Electron, Scanning
15.
Photochem Photobiol Sci ; 23(6): 1129-1142, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38734995

ABSTRACT

Bacterial infections are a global health concern, particularly due to the increasing resistance of bacteria to antibiotics. Multi-drug resistance (MDR) is a considerable challenge, and novel approaches are needed to treat bacterial infections. Photodynamic inactivation (PDI) of microorganisms is increasingly recognized as an effective method to inactivate a broad spectrum of bacteria and overcome resistance mechanisms. This study presents the synthesis of a new cationic 5,15-di-imidazolyl porphyrin derivative and the impact of n-octanol/water partition coefficient (logP) values of this class of photosensitizers on PDI efficacy of Escherichia coli. The derivative with logP = -0.5, IP-H-OH2+, achieved a remarkable 3 log CFU reduction of E. coli at 100 nM with only 1.36 J/cm2 light dose at 415 nm, twice as effective as the second-best porphyrin IP-H-Me2+, of logP = -1.35. We relate the rapid uptake of IP-H-OH2+ by E. coli to improved PDI and the very low uptake of a fluorinated derivative, IP-H-CF32+, logP ≈ 1, to its poor performance. Combination of PDI with cinnamaldehyde, a major component of the cinnamon plant known to alter bacteria cell membranes, offered synergic inactivation of E. coli (7 log CFU reduction), using 50 nM of IP-H-OH2+ and just 1.36 J/cm2 light dose. The success of combining PDI with this natural compound broadens the scope of therapies for MDR infections that do not add drug resistance. In vivo studies on a mouse model of wound infection showed the potential of cationic 5,15-di-imidazolyl porphyrins to treat clinically relevant infected wounds.


Subject(s)
Acrolein , Anti-Bacterial Agents , Escherichia coli , Imidazoles , Photosensitizing Agents , Porphyrins , Escherichia coli/drug effects , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/chemical synthesis , Porphyrins/pharmacology , Porphyrins/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Acrolein/analogs & derivatives , Acrolein/pharmacology , Acrolein/chemistry , Imidazoles/chemistry , Imidazoles/pharmacology , Imidazoles/chemical synthesis , Cations/chemistry , Cations/pharmacology , Microbial Sensitivity Tests , Animals , Mice , Drug Synergism , Photochemotherapy
16.
Photodiagnosis Photodyn Ther ; 47: 104196, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38710260

ABSTRACT

SIGNIFICANCE: Hemoporfin-mediated photodynamic therapy (HMME-PDT) has been recognized as a safe and effective treatment for port wine stain (PWS). However, some patients show limited improvement even after multiple treatments. Herein, we aim to explore the effect of autophagy on HMME-PDT in human umbilical vein endothelial cells (HUVECs), so as to provide theoretical basis and treatment strategies to enhance clinical effectiveness. METHODS: Establish the in vitro HMME-PDT system by HUVECs. Apoptosis and necrosis were identified by Annexin Ⅴ-FITC/PI flow cytometry, and autophagy flux was detected by monitoring RFP-GFP-LC3 under the fluorescence microscope. Hydroxychloroquine and rapamycin were employed in the mechanism study. Specifically, the certain genes and proteins were qualified by qPCR and Western Blot, respectively. The cytotoxicity was measured by CCK-8, VEGF-A secretion was determined by ELISA, and the tube formation of HUVECs was observed by angiogenesis assay. RESULTS: In vitro experiments revealed that autophagy and apoptosis coexisted in HUVECs treated by HMME-PDT. Apoptosis was dominant in early stage, while autophagy gradually increased in the middle and late stage. AMPK, AKT and mTOR participated in the regulation of autophagy induced by HMME-PDT, in which AMPK was positive regulation, while AKT and mTOR were negative regulation. Hydroxychloroquine could not inhibit HMME-PDT-induced autophagy, but capable of blocking the fusion of autophagosomes with lysosome. Rapamycin might cooperate with HMME-PDT to enhance autophagy in HUVECs, leading to increased cytotoxicity, reduced VEGF-A secretion, and weakened angiogenesis ability. CONCLUSIONS: Both autophagy and apoptosis contribute to HMME-PDT-induced HUVECs death. Pretreatment of HUVECs with rapamycin to induce autophagy might enhance the photodynamic killing effect of HMME-PDT on HUVECs. The combination of Rapamycin and HMME-PDT is expected to further improve the clinical efficacy.


Subject(s)
Apoptosis , Autophagy , Human Umbilical Vein Endothelial Cells , Photochemotherapy , Photosensitizing Agents , Sirolimus , Humans , Human Umbilical Vein Endothelial Cells/drug effects , Photochemotherapy/methods , Autophagy/drug effects , Photosensitizing Agents/pharmacology , Apoptosis/drug effects , Sirolimus/pharmacology , Hydroxychloroquine/pharmacology , Porphyrins/pharmacology , Vascular Endothelial Growth Factor A/metabolism
17.
Photodiagnosis Photodyn Ther ; 47: 104200, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38723757

ABSTRACT

BACKGROUND: Photodynamic therapy (PDT) is used for the treatment of centrally-located early lung cancers (CLELCs) and is recommended for tumors ≤ 1.0 cm in diameter. We previously reported that PDT using talaporfin sodium, second-generation photosensitizer, for tumors > 1.0 cm but ≤ 2.0 cm in diameter was able to achieve a therapeutic outcome comparable to that of tumors with a diameter of ≤ 1.0 cm. However, the effectiveness of PDT using talaporfin sodium for tumors > 2.0 cm in diameter remains unclear. We conducted a retrospective analysis of cases in which PDT was performed for flat-type CLELCs with tumor diameters of > 2.0 cm. METHODS: We retrospectively analyzed seven cases (eight lesions) with tumor diameters > 2.0 cm and no evidence of extracartilaginous invasion or lymph node metastasis. RESULTS: All the patients underwent multiple PDT sessions. The PDT treatment results over the study period were partial response in one case (14.3 %), stable disease (SD) in three cases (42.9 %), and progressive disease (PD) in three cases (42.9 %). At the time of writing this report, five of seven cases (71.4 %) are still undergoing treatment. The duration of SD-the time from the start of treatment until the criteria for PD were met (SD or better maintained)-ranged from 7 to 52 months (mean, 25.3 months). CONCLUSIONS: "Maintenance PDT" for CLELCs > 2.0 cm in diameter has the potential to inhibit tumor progression in the long term while maintaining quality of life, rather than simply aiming only for a quick radical cure.


Subject(s)
Lung Neoplasms , Photochemotherapy , Photosensitizing Agents , Porphyrins , Humans , Photochemotherapy/methods , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Photosensitizing Agents/therapeutic use , Male , Aged , Female , Retrospective Studies , Middle Aged , Porphyrins/therapeutic use , Aged, 80 and over , Treatment Outcome
18.
J Photochem Photobiol B ; 256: 112928, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38723545

ABSTRACT

INTRODUCTION: Emerging antibiotic resistance among bacterial pathogens has forced an urgent need for alternative non-antibiotic strategies development that could combat drug resistant-associated infections. Suppression of virulence of ESKAPE pathogens' by targeting multiple virulence traits provides a promising approach. OBJECTIVES: Here we propose an iron-blocking antibacterial therapy based on a cationic heme-mimetic gallium porphyrin (GaCHP), which antibacterial efficacy could be further enhanced by photodynamic inactivation. METHODS: We used gallium heme mimetic porphyrin (GaCHP) excited with light to significantly reduce microbial viability and suppress both the expression and biological activity of several virulence traits of both Gram-positive and Gram-negative ESKAPE representatives, i.e., S. aureus and P. aeruginosa. Moreover, further improvement of the proposed strategy by combining it with routinely used antimicrobials to resensitize the microbes to antibiotics and provide enhanced bactericidal efficacy was investigated. RESULTS: The proposed strategy led to substantial inactivation of critical priority pathogens and has been evidenced to suppress the expression and biological activity of multiple virulence factors in S. aureus and P. aeruginosa. Finally, the combination of GaCHP phototreatment and antibiotics resulted in promising strategy to overcome antibiotic resistance of the studied microbes and to enhance disinfection of drug resistant pathogens. CONCLUSION: Lastly, considering high safety aspects of the proposed treatment toward host cells, i.e., lack of mutagenicity, no dark toxicity and mild phototoxicity, we describe an efficient alternative that simultaneously suppresses the functionality of multiple virulence factors in ESKAPE pathogens.


Subject(s)
Anti-Bacterial Agents , Gallium , Heme , Photosensitizing Agents , Porphyrins , Pseudomonas aeruginosa , Staphylococcus aureus , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Gallium/chemistry , Gallium/pharmacology , Porphyrins/chemistry , Porphyrins/pharmacology , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Heme/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Virulence/drug effects , Microbial Sensitivity Tests , Light , Drug Resistance, Bacterial/drug effects
19.
J Med Chem ; 67(11): 9054-9068, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38781403

ABSTRACT

Molecular hybridization is a well-established strategy for developing new drugs. In the pursuit of promising photosensitizers (PSs) with enhanced photodynamic therapy (PDT) efficiency, a series of novel 5-fluorouracil (5FU) gallium corrole conjugates (1-Ga-4-Ga) were designed and synthesized by hybridizing a chemotherapeutic drug and PSs. Their photodynamic antitumor activity was also evaluated. The most active complex (2-Ga) possesses a low IC50 value of 0.185 µM and a phototoxic index of 541 against HepG2 cells. Additionally, the 5FU-gallium corrole conjugate (2-Ga) exhibited a synergistic increase in cytotoxicity under irradiation. Excitedly, treatment of HepG2 tumor-bearing mice with 2-Ga under irradiation could completely ablate tumors without harming normal tissues. 2-Ga-mediated PDT could disrupt mitochondrial function, cause cell cycle arrest in the sub-G1 phase, and activate the cell apoptosis pathway by upregulating the cleaved PARP expression and the Bax/Bcl-2 ratios. This work provides a useful strategy for the design of new corrole-based chemo-photodynamic therapy drugs.


Subject(s)
Apoptosis , Fluorouracil , Gallium , Photochemotherapy , Photosensitizing Agents , Porphyrins , Fluorouracil/pharmacology , Fluorouracil/chemistry , Fluorouracil/therapeutic use , Humans , Gallium/chemistry , Gallium/pharmacology , Animals , Porphyrins/pharmacology , Porphyrins/chemistry , Porphyrins/therapeutic use , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/therapeutic use , Mice , Apoptosis/drug effects , Hep G2 Cells , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Mice, Inbred BALB C , Mice, Nude
20.
BMC Cancer ; 24(1): 587, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38741073

ABSTRACT

YAP and TAZ, the Hippo pathway terminal transcriptional activators, are frequently upregulated in cancers. In tumor cells, they have been mainly associated with increased tumorigenesis controlling different aspects from cell cycle regulation, stemness, or resistance to chemotherapies. In fewer cases, they have also been shown to oppose cancer progression, including by promoting cell death through the action of the p73/YAP transcriptional complex, in particular after chemotherapeutic drug exposure. Using HCT116 cells, we show here that oxaliplatin treatment led to core Hippo pathway down-regulation and nuclear accumulation of TAZ. We further show that TAZ was required for the increased sensitivity of HCT116 cells to oxaliplatin, an effect that appeared independent of p73, but which required the nuclear relocalization of TAZ. Accordingly, Verteporfin and CA3, two drugs affecting the activity of YAP and TAZ, showed antagonistic effects with oxaliplatin in co-treatments. Importantly, using several colorectal cell lines, we show that the sensitizing action of TAZ to oxaliplatin is dependent on the p53 status of the cells. Our results support thus an early action of TAZ to sensitize cells to oxaliplatin, consistent with a model in which nuclear TAZ in the context of DNA damage and p53 activity pushes cells towards apoptosis.


Subject(s)
Antineoplastic Agents , Colonic Neoplasms , Hippo Signaling Pathway , Organoplatinum Compounds , Oxaliplatin , Protein Serine-Threonine Kinases , Signal Transduction , Trans-Activators , Transcription Factors , Transcriptional Coactivator with PDZ-Binding Motif Proteins , Tumor Suppressor Protein p53 , Humans , Oxaliplatin/pharmacology , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Colonic Neoplasms/drug therapy , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Colonic Neoplasms/genetics , Trans-Activators/metabolism , Trans-Activators/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , HCT116 Cells , Signal Transduction/drug effects , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Organoplatinum Compounds/pharmacology , Organoplatinum Compounds/therapeutic use , Antineoplastic Agents/pharmacology , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Drug Resistance, Neoplasm/genetics , Tumor Suppressor Proteins/metabolism , Tumor Suppressor Proteins/genetics , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Verteporfin/pharmacology , Verteporfin/therapeutic use , Cell Line, Tumor , Tumor Protein p73/metabolism , Tumor Protein p73/genetics , YAP-Signaling Proteins/metabolism , Porphyrins/pharmacology , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Gene Expression Regulation, Neoplastic/drug effects , Apoptosis/drug effects
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