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Journal of Nanobiotechnology Jun 2024Hypoxia-activated prodrug (HAP) is a promising candidate for highly tumor-specific chemotherapy. However, the oxygenation heterogeneity and dense extracellular matrix...
BACKGROUND
Hypoxia-activated prodrug (HAP) is a promising candidate for highly tumor-specific chemotherapy. However, the oxygenation heterogeneity and dense extracellular matrix (ECM) of tumor, as well as the potential resistance to chemotherapy, have severely impeded the resulting overall efficacy of HAP.
RESULTS
A HAP potentiating strategy is proposed based on ultrasound responsive nanodroplets (PTP@PLGA), which is composed of protoporphyrin (PpIX), perfluoropropane (PFP) and a typical HAP, tirapazamine (TPZ). The intense vaporization of PFP upon ultrasound irradiation can magnify the sonomechanical effect, which loosens the ECM to promote the penetration of TPZ into the deep hypoxic region. Meanwhile, the PpIX enabled sonodynamic effect can further reduce the oxygen level, thus activating the TPZ in the relatively normoxic region as well. Surprisingly, abovementioned ultrasound effect also results in the downregulation of the stemness of cancer cells, which is highly associated with drug-refractoriness.
CONCLUSIONS
This work manifests an ideal example of ultrasound-based nanotechnology for potentiating HAP and also reveals the potential acoustic effect of intervening cancer stem-like cells.
Topics: Humans; Tirapazamine; Protoporphyrins; Fluorocarbons; Prodrugs; Cell Line, Tumor; Nanoparticles; Neoplastic Stem Cells; Antineoplastic Agents; Ultrasonic Waves; Animals; Extracellular Matrix; Mice; Neoplasms
PubMed: 38907270
DOI: 10.1186/s12951-024-02623-0 -
Bioorganic & Medicinal Chemistry Jun 2024The antimicrobial activity of new acid-functionalized porphyrins, with or without ultra-high irradiance, was investigated. Antibacterial efficacy was evaluated against...
Synthesis and characterization of new acid-functionalized porphyrins displaying antimicrobial activity against gram positive bacteria, yeasts and filamentous fungi with or without ultra-high irradiance.
The antimicrobial activity of new acid-functionalized porphyrins, with or without ultra-high irradiance, was investigated. Antibacterial efficacy was evaluated against Staphylococcus aureus (methicillin-resistant or methicillin-sensitive strains) and antifungal efficacy was evaluated against the yeast Candida albicans and the filamentous fungi Aspergillus fumigatus. Overall, the porphyrins tested are more effective against S. aureus. The best results were obtained with zinc diacid porphyrins 4 and 5 after only 3 min of ultra-high irradiation (500 mW/cm, 405 nm), demonstrating that acid-functionalized porphyrins are promising as novel antimicrobial drugs for surface disinfection.
PubMed: 38906069
DOI: 10.1016/j.bmc.2024.117810 -
MSphere Jun 2024Epitopes from the cell surface proteins Fba and Met6 are putative vaccine targets for invasive candidiasis. Here, we describe a vaccine approach in which short...
UNLABELLED
Epitopes from the cell surface proteins Fba and Met6 are putative vaccine targets for invasive candidiasis. Here, we describe a vaccine approach in which short peptides derived from Fba and Met6 are used in spontaneous nanoliposome antigen particle (SNAP) format. SNAP was enabled by the interaction of cobalt porphyrin phospholipid in liposomes with three histidine residues on the N-terminus of synthetic short peptide immunogens from Fba (F-SNAP), Met6 (M-SNAP), or bivalent Fba and Met6 (FM-SNAP). Liposomes were adjuvanted with synthetic monophosphoryl lipid and QS-21. In mice, immunization with F-SNAP, M-SNAP, or FM-SNAP induced antigen-specific IgG responses and mixed Th1/Th2 immunity. The duplex FM-SNAP vaccine elicited stronger antibody responses against each peptide, even at order-of-magnitude lower peptide dosing than a comparable adjuvanted, conjugate vaccine. Enzyme-linked immunosorbent spot analysis revealed the induction of antigen-specific, cytokine-producing T cells. Compared to F-SNAP or M-SNAP, higher production of TNFα, IL-2, and IFNγ was observed with re-stimulation of splenocytes from bivalent FM-SNAP-immunized mice. When vaccinated BALB/c mice were challenged with , analysis of the fungal burden in the kidneys showed that SNAP vaccination protected from disseminated candidiasis. In a lethal fungal exposure model in A/J mice, F-SNAP, M-SNAP, and FM-SNAP vaccination protected mice from candidiasis challenge. Together, these results show that further investigation into the SNAP adjuvant platform is warranted using Fba and Met6 epitopes for a pan- peptide vaccine that provides multifaceted protective immune responses.
IMPORTANCE
This study introduces a promising vaccine strategy against invasive candidiasis, a severe fungal infection, by targeting specific peptides on the surface of . Using a novel approach called spontaneous nanoliposome antigen particle (SNAP), we combined peptides from two key proteins, Fba and Met6, into a vaccine. This vaccine induced robust immune responses in mice, including the production of protective antibodies and the activation of immune cells. Importantly, mice vaccinated with SNAP were shielded from disseminated candidiasis in experiments. These findings highlight a potential avenue for developing a broad-spectrum vaccine against infections, which could significantly improve outcomes for patients at risk of these often deadly fungal diseases.
PubMed: 38904363
DOI: 10.1128/msphere.00189-24 -
RSC Advances Jun 2024A supramolecular complex μ--tetra(4-pyridyl) porphyrinate nickel(ii)tetrakis[bis(bipyridine)(chloro)ruthenium(ii)] ([NiTPyP{Ru(bipy)Cl}]) was intercalated into the...
Glassy carbon electrode modified with a film of tetraruthenated nickel(ii) porphyrin located in natural smectite clay's interlayer for the simultaneous sensing of dopamine, acetaminophen and tryptophan.
A supramolecular complex μ--tetra(4-pyridyl) porphyrinate nickel(ii)tetrakis[bis(bipyridine)(chloro)ruthenium(ii)] ([NiTPyP{Ru(bipy)Cl}]) was intercalated into the interlayer space of natural smectite clay (shortened as Ba) collected in a Cameroonian deposit at Bagba hill. Physicochemical characterization of the resulting material using ultraviolet-visible spectroscopy (UV-vis), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) confirmed the intercalation of the porphyrin within the interlayer space of the clay. The intercalated clay was then used to form a stable thin film onto a glassy carbon electrode (GCE) by drop casting a suspension of the hybrid material. The GCE modified with the intercalated organoclay endowed the electrode with a larger electrochemically active surface area, good stability, high selectivity, and sensitivity toward dopamine (DA), acetaminophen (AC) and tryptophan (Trp). In addition, it was observed that the modified electrodes exhibited good and pH-dependent electrocatalytic properties toward these analytes. The simultaneous determination of DA, AC and Trp at [NiTPyP{Ru(bipy)Cl}]-Ba/GCE was thus possible without the interference of one analyte on the others, and the resulting calibration curve exhibits two segments for the three analytes. For DA, AC and Trp, the detection limits were found to be 0.8 μM, 0.3 μM and 0.3 μM, respectively. The [NiTPyP{Ru(bipy)Cl}]-Ba/GCE modified electrodes were successfully applied for the determination of AC in Paracetamol, a commercial product, and Trp in real pharmaceutical formulation samples.
PubMed: 38895529
DOI: 10.1039/d4ra03253e -
Molecules (Basel, Switzerland) May 2024Developing clinically meaningful nanomedicines for cancer therapy requires the drugs to be effective, safe, simple, cheap, and easy to store. In the present work, we...
Developing clinically meaningful nanomedicines for cancer therapy requires the drugs to be effective, safe, simple, cheap, and easy to store. In the present work, we report that a simple cationic Fe(III)-rich salt of [FeCl(TMPPH)][FeCl] () exhibits a superior anticancer performance on a broad spectrum of cancer cell lines, including breast, colorectal cancer, liver, pancreatic, prostate, and gastric cancers, with half maximal inhibitory concentration (IC) values in the range of 0.098-3.97 μM (0.066-2.68 μg mL), comparable to the best-reported medicines. can form stand-alone nanoparticles in water without the need for extra surface modification or organic-solvent-assisted antisolvent precipitation. Critically, is TME-responsive (TME = tumor microenvironment), and can only elicit its function in the TME with overexpressed HO, converting HO to the cytotoxic •OH to oxidize the phospholipid of the cancer cell membrane, causing ferroptosis, a programmed cell death process of cancer cells.
Topics: Humans; Ferroptosis; Cell Line, Tumor; Nanomedicine; Antineoplastic Agents; Nanoparticles; Ferric Compounds; Tumor Microenvironment; Hydrogen Peroxide; Cell Survival; Neoplasms
PubMed: 38893373
DOI: 10.3390/molecules29112495 -
Molecules (Basel, Switzerland) May 2024Cytochrome P450s (P450s), a superfamily of heme-containing enzymes, existed in animals, plants, and microorganisms. P450s can catalyze various regional and... (Review)
Review
Cytochrome P450s (P450s), a superfamily of heme-containing enzymes, existed in animals, plants, and microorganisms. P450s can catalyze various regional and stereoselective oxidation reactions, which are widely used in natural product biosynthesis, drug metabolism, and biotechnology. In a typical catalytic cycle, P450s use redox proteins or domains to mediate electron transfer from NAD(P)H to heme iron. Therefore, the main factors determining the catalytic efficiency of P450s include not only the P450s themselves but also their redox-partners and electron transfer pathways. In this review, the electron transfer pathway engineering strategies of the P450s catalytic system are reviewed from four aspects: cofactor regeneration, selection of redox-partners, P450s and redox-partner engineering, and electrochemically or photochemically driven electron transfer.
Topics: Cytochrome P-450 Enzyme System; Electron Transport; Protein Engineering; Oxidation-Reduction; Heme; Animals; Humans
PubMed: 38893355
DOI: 10.3390/molecules29112480 -
Molecules (Basel, Switzerland) May 2024Iron porphyrins are known to provide CH as an eight-electron reduction product of CO in a photochemical reaction. However, there are still some aspects of the reaction...
Iron porphyrins are known to provide CH as an eight-electron reduction product of CO in a photochemical reaction. However, there are still some aspects of the reaction mechanism that remain unclear. In this study, we synthesized iron porphyrin dimers and carried out the photochemical CO reduction reactions in -dimethylacetamide (DMA) containing a photosensitizer in the presence of 1,3-dimethyl-2-phenyl-2,3-dihydro-1-benzo[d]imidazole (BIH) as an electron donor. We found that, despite a low catalytic turnover number, CH was produced only when these porphyrins were facing each other. The close proximity of the cyclic dimers, distinguishing them from a linear Fe porphyrin dimer and monomers, induced multi-electron CO reduction, emphasizing the unique role of their structural arrangement in CH formation.
PubMed: 38893329
DOI: 10.3390/molecules29112453 -
International Journal of Molecular... May 2024Anoctamin1 (ANO1), a calcium-activated chloride channel, is overexpressed in a variety of cancer cells, including prostate cancer, and is involved in cancer cell...
Anoctamin1 (ANO1), a calcium-activated chloride channel, is overexpressed in a variety of cancer cells, including prostate cancer, and is involved in cancer cell proliferation, migration, and invasion. Inhibition of ANO1 in these cancer cells exhibits anticancer effects. In this study, we conducted a screening to identify novel ANO1 inhibitors with anticancer effects using PC-3 human prostate carcinoma cells. Screening of 2978 approved and investigational drugs revealed that hemin is a novel ANO1 inhibitor with an IC value of 0.45 μM. Notably, hemin had no significant effect on intracellular calcium signaling and cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic AMP (cAMP)-regulated chloride channel, and it showed a weak inhibitory effect on ANO2 at 3 μM, a concentration that completely inhibits ANO1. Interestingly, hemin also significantly decreased ANO1 protein levels and strongly inhibited the cell proliferation and migration of PC-3 cells in an ANO1-dependent manner. Furthermore, it strongly induced caspase-3 activation, PARP degradation, and apoptosis in PC-3 cells. These findings suggest that hemin possesses anticancer properties via ANO1 inhibition and could be considered for development as a novel treatment for prostate cancer.
Topics: Humans; Anoctamin-1; Male; Hemin; Prostatic Neoplasms; Cell Proliferation; Neoplasm Proteins; Cell Movement; Apoptosis; Antineoplastic Agents; Cell Line, Tumor; PC-3 Cells
PubMed: 38892219
DOI: 10.3390/ijms25116032 -
International Journal of Molecular... May 2024New β-amino-substituted porphyrin derivatives bearing carboxy groups were synthesized and their performance as sensitizers in dye-sensitized solar cells (DSSC) was...
New β-amino-substituted porphyrin derivatives bearing carboxy groups were synthesized and their performance as sensitizers in dye-sensitized solar cells (DSSC) was evaluated. The new compounds were obtained in good yields (63-74%) through nucleophilic aromatic substitution reactions with 3-sulfanyl- and 4-sulfanylbenzoic acids. Although the electrochemical studies indicated suitable HOMO and LUMO energy levels for use in DSSC, the devices fabricated with these compounds revealed a low power conversion efficiency (PCE) that is primarily due to the low open-circuit voltage (V) and short-circuit current density (J) values.
Topics: Porphyrins; Solar Energy
PubMed: 38892167
DOI: 10.3390/ijms25115979 -
International Journal of Molecular... May 2024The impact of age on mesenchymal stromal cell (MSC) characteristics has been well researched. However, increased age is concomitant with increased prevalence of...
The impact of age on mesenchymal stromal cell (MSC) characteristics has been well researched. However, increased age is concomitant with increased prevalence of polypharmacy. This adjustable factor may have further implications for the functionality of MSCs and the effectiveness of autologous MSC procedures. We applied hyperspectral microscopy of cell autofluorescence-a non-invasive imaging technique used to characterise cytometabolic heterogeneity-to identify changes in the autofluorescence signals of MSCs from (1) young mice, (2) old mice, (3) young mice randomised to receive polypharmacy (9-10 weeks of oral therapeutic doses of simvastatin, metoprolol, oxycodone, oxybutynin and citalopram), and (4) old mice randomised to receive polypharmacy. Principal Component Analysis and Logistic Regression Analysis were used to assess alterations in spectral and associated metabolic characteristics. Modelling demonstrated that cells from young mice receiving polypharmacy had less NAD(P)H and increased porphyrin relative to cells from old control mice, allowing for effective separation of the two groups (AUC of ROC curve > 0.94). Similarly, cells from old polypharmacy mice were accurately separated from those from young controls due to lower levels of NAD(P)H ( < 0.001) and higher porphyrin ( < 0.001), allowing for an extremely accurate logistic regression (AUC of ROC curve = 0.99). This polypharmacy regimen may have a more profound impact on MSCs than ageing, and can simultaneously reduce optical redox ratio (ORR) and increase porphyrin levels. This has implications for the use of autologous MSCs for older patients with chronic disease.
Topics: Animals; Mesenchymal Stem Cells; Mice; Polypharmacy; Aging; Male; Optical Imaging; NADP
PubMed: 38892017
DOI: 10.3390/ijms25115830