-
Biosensors May 2024Biosensors function as sophisticated devices, converting biochemical reactions into electrical signals. Contemporary emphasis on developing biosensor devices with... (Review)
Review
Biosensors function as sophisticated devices, converting biochemical reactions into electrical signals. Contemporary emphasis on developing biosensor devices with refined sensitivity and selectivity is critical due to their extensive functional capabilities. However, a significant challenge lies in the binding affinity of biosensors to biomolecules, requiring adept conversion and amplification of interactions into various signal modalities like electrical, optical, gravimetric, and electrochemical outputs. Overcoming challenges associated with sensitivity, detection limits, response time, reproducibility, and stability is essential for efficient biosensor creation. The central aspect of the fabrication of any biosensor is focused towards forming an effective interface between the analyte electrode which significantly influences the overall biosensor quality. Polymers and macromolecular systems are favored for their distinct properties and versatile applications. Enhancing the properties and conductivity of these systems can be achieved through incorporating nanoparticles or carbonaceous moieties. Hybrid composite materials, possessing a unique combination of attributes like advanced sensitivity, selectivity, thermal stability, mechanical flexibility, biocompatibility, and tunable electrical properties, emerge as promising candidates for biosensor applications. In addition, this approach enhances the electrochemical response, signal amplification, and stability of fabricated biosensors, contributing to their effectiveness. This review predominantly explores recent advancements in utilizing macrocyclic and macromolecular conjugated systems, such as phthalocyanines, porphyrins, polymers, etc. and their hybrids, with a specific focus on signal amplification in biosensors. It comprehensively covers synthetic strategies, properties, working mechanisms, and the potential of these systems for detecting biomolecules like glucose, hydrogen peroxide, uric acid, ascorbic acid, dopamine, cholesterol, amino acids, and cancer cells. Furthermore, this review delves into the progress made, elucidating the mechanisms responsible for signal amplification. The Conclusion addresses the challenges and future directions of macromolecule-based hybrids in biosensor applications, providing a concise overview of this evolving field. The narrative emphasizes the importance of biosensor technology advancement, illustrating the role of smart design and material enhancement in improving performance across various domains.
Topics: Biosensing Techniques; Nanoparticles; Polymers; Humans; Electrochemical Techniques
PubMed: 38920581
DOI: 10.3390/bios14060277 -
ACS Omega Jun 2024Water electrolysis for clean hydrogen production requires high-activity, high-stability, and low-cost catalysts for its particularly sluggish half-reaction, the oxygen...
Water electrolysis for clean hydrogen production requires high-activity, high-stability, and low-cost catalysts for its particularly sluggish half-reaction, the oxygen evolution reaction (OER). Currently, the most promising of such catalysts working in alkaline conditions is a core-shell nanostructure, NiFe@NC, whose Fe-doped Ni (NiFe) nanoparticles are encapsulated and interconnected by N-doped graphitic carbon (NC) layers, but the exact OER mechanism of these catalysts is still unclear, and even the location of the OER active site, either on the core side or on the shell side, is still debated. Therefore, we herein derive a plausible active-site model for each side based on various experimental evidence and density functional theory calculations and then build OER free-energy diagrams on both sides to determine the active-site location. The core-side model is an FeO-type (rather than NiO-type) active site where an Fe atom sits on Ni oxide layers grown on top of the core surface during catalyst activation, whose facile dissolution provides an explanation for the activity loss of such catalysts directly exposed to the electrolyte. The shell-side model is a NiN-type (rather than FeN-type) active site where a Ni atom is intercalated into the porphyrin-like NC site of the NC shell during catalyst synthesis. Their OER free-energy diagrams indicate that both sites require similar amounts of overpotentials, despite a complete shift in their potential-determining steps, i.e., the final O evolution from the oxophilic Fe on the core and the initial OH adsorption to the hydrophobic shell. We conclude that the major active sites are located on the core, but the NC shell not only protects the vulnerable FeO active sites on the core from the electrolyte but also provides independent active sites, owing to the N doping.
PubMed: 38911812
DOI: 10.1021/acsomega.3c09920 -
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