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1.
Anal Chem ; 96(19): 7687-7696, 2024 May 14.
Article En | MEDLINE | ID: mdl-38693877

Smart theranostic nanoprobes with the integration of multiple therapeutic modalities are preferred for precise diagnosis and efficient therapy of tumors. However, it remains a big challenge to arrange the imaging and two or more kinds of therapeutic agents without weakening the intended performances. In addition, most existing fluorescence (FL) imaging agents suffer from low spatiotemporal resolution due to the short emission wavelength (<900 nm). Here, novel three-in-one Ag2S quantum dot (QD)-based smart theranostic nanoprobes were proposed for in situ ratiometric NIR-II FL imaging-guided ion/gas combination therapy of tumors. Under the acidic tumor microenvironment, three-in-one Ag2S QDs underwent destructive degradation, generating toxic Ag+ and H2S. Meanwhile, their FL emission at 1270 nm was weakened. Upon introduction of a downconversion nanoparticle (DCNP) as the delivery carrier and NIR-II FL reference signal unit, the formed Ag2S QD-based theranostic nanoprobes could achieve precise diagnosis of tumors through ratiometric NIR-II FL signals. Also, the generated Ag+ and H2S enabled specific ion/gas combination therapy toward tumors. By combining the imaging and therapeutic functions, three-in-one Ag2S QDs may open a simple yet reliable avenue to design theranostic nanoprobes.


Optical Imaging , Quantum Dots , Silver Compounds , Quantum Dots/chemistry , Silver Compounds/chemistry , Humans , Animals , Mice , Infrared Rays , Theranostic Nanomedicine , Hydrogen Sulfide/analysis , Hydrogen Sulfide/chemistry , Hydrogen-Ion Concentration
2.
ACS Appl Mater Interfaces ; 16(21): 27114-27126, 2024 May 29.
Article En | MEDLINE | ID: mdl-38747624

The practical application of photodynamic therapy (PDT) demands targeted and activatable photosensitizers to mitigate off-target phototoxicity common in "always on" photosensitizers during light exposure. Herein, a cyclometalated iridium complex-based activatable photodynamic molecular hybrid, Cy-Ir-7-nitrobenzofurazan (NBD), is demonstrated as a biomedicine for molecular precision. This design integrates a hydrogen sulfide (H2S)-responsive NBD unit with a hydroxy-appended iridium complex, Cy-Ir-OH. In normal physiological conditions, the electron-rich Ir metal center exerts electron transfer to the NBD unit, quenches the excited state dynamics, and establishes a PDT-off state. Upon exposure to H2S, Cy-Ir-NBD activates into the potent photosensitizer Cy-Ir-OH through nucleophilic substitution. This mechanism ensures exceptional specificity, enabling targeted phototherapy in H2S-rich cancer cells. Additionally, we observed that Cy-Ir-NBD-induced H2S depletion disrupts S-sulfhydration of the glyceraldehyde-3-phosphate dehydrogenase enzyme, impairing glycolysis and ATP production in the cellular milieu. This sequential therapeutic process of Cy-Ir-NBD is governed by the positively charged central iridium ion that ensures mitochondria-mediated apoptosis in cancer cells. Dual-modality SERS and fluorescence imaging validate apoptotic events, highlighting Cy-Ir-NBD as an advanced theranostic molecular entity for activatable PDT. Finally, as a proof of concept, clinical assessment is evaluated with the blood samples of breast cancer patients and healthy volunteers, based on their H2S overexpression capability through SERS and fluorescence, revealing Cy-Ir-NBD to be a promising predictor for PDT activation in advanced cancer phototherapy.


Glycolysis , Hydrogen Sulfide , Iridium , Photochemotherapy , Photosensitizing Agents , Humans , Iridium/chemistry , Iridium/pharmacology , Hydrogen Sulfide/chemistry , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Glycolysis/drug effects , Neoplasms/drug therapy , Neoplasms/diagnostic imaging , Cell Line, Tumor , Fluorescence
3.
J Med Chem ; 67(9): 7431-7442, 2024 May 09.
Article En | MEDLINE | ID: mdl-38664896

Since hydrogen sulfide (H2S) is an important endogenous gaseous mediator, therapeutic manipulation of H2S is promising for anticancer treatment. In this work, we develop a novel theranostic nanoplatform with H2S-specific and photocontrolled synergistic activation for imaging-guided H2S depletion and downregulation along with promoted photothermal therapy. Such a nanoplatform is fabricated by integration of a H2S-responsive molecule probe that can generate a cystathionine-ß-synthase (CBS) inhibitor AOAA and a photothermal transducer into an NIR-light-responsive container. Our nanoplatform can turn on NIR fluorescence specifically in H2S-rich cancers, guiding further laser irradiation. Furthermore, prominent conversion of photoenergy into heat guarantees special container melting with controllable AOAA release for H2S-level downregulation. This smart regulation of the endogenous H2S level amplifies the PTT therapeutic effect, successfully suppressing colorectal tumor in living mice under NIR fluorescence imaging guidance. Thus, we believe that this nanoplatform may provide a powerful tool toward H2S-concerned cancer treatment with an optimized diagnostic and therapeutic effect.


Colorectal Neoplasms , Down-Regulation , Hydrogen Sulfide , Photothermal Therapy , Hydrogen Sulfide/metabolism , Hydrogen Sulfide/chemistry , Animals , Photothermal Therapy/methods , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/therapy , Colorectal Neoplasms/pathology , Humans , Mice , Down-Regulation/drug effects , Cystathionine beta-Synthase/metabolism , Cystathionine beta-Synthase/antagonists & inhibitors , Optical Imaging , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Mice, Inbred BALB C , Mice, Nude , Nanoparticles/chemistry , Infrared Rays , Cell Line, Tumor , Theranostic Nanomedicine/methods
4.
Chem Commun (Camb) ; 60(37): 4918-4921, 2024 May 02.
Article En | MEDLINE | ID: mdl-38628069

To avoid the unexpected aggregation and reduce the cytotoxicity of nanomaterials as optical probes in cell imaging applications, we propose a programmed DNA-cube as a carrier for silver nanoparticles (Ag NPs) to construct a specific hydrogen sulfide (H2S) responsive platform (Ag NP@DNA-cube) for diagnosing colorectal cancer (CRC) in this study. The DNA-cube maintains good dispersion of Ag NPs while providing excellent biocompatibility. Based on the characteristic overexpression of endogenous H2S in CRC cells, the Ag NPs are etched by H2S within target cells into silver sulfide quantum dots, thereby selectively illuminating the target cells. The Ag NP@DNA-cube exhibits a specific fluorescence response to CRC cells and achieves satisfactory imaging.


Colorectal Neoplasms , DNA , Hydrogen Sulfide , Metal Nanoparticles , Silver , Hydrogen Sulfide/analysis , Hydrogen Sulfide/chemistry , Humans , Metal Nanoparticles/chemistry , Colorectal Neoplasms/pathology , Silver/chemistry , DNA/chemistry , Optical Imaging , Quantum Dots/chemistry , Cell Line, Tumor
5.
Sci Rep ; 14(1): 9364, 2024 04 23.
Article En | MEDLINE | ID: mdl-38654065

The escalating drug resistance among microorganisms underscores the urgent need for innovative therapeutic strategies and a comprehensive understanding of bacteria's defense mechanisms against oxidative stress and antibiotics. Among the recently discovered barriers, the endogenous production of hydrogen sulfide (H2S) via the reverse transsulfuration pathway, emerges as a noteworthy factor. In this study, we have explored the catalytic capabilities and crystal structure of cystathionine γ-lyase from Pseudomonas aeruginosa (PaCGL), a multidrug-opportunistic pathogen chiefly responsible for nosocomial infections. In addition to a canonical L-cystathionine hydrolysis, PaCGL efficiently catalyzes the production of H2S using L-cysteine and/or L-homocysteine as alternative substrates. Comparative analysis with the human enzyme and counterparts from other pathogens revealed distinct structural features within the primary enzyme cavities. Specifically, a distinctly folded entrance loop could potentially modulate the access of substrates and/or inhibitors to the catalytic site. Our findings offer significant insights into the structural evolution of CGL enzymes across different pathogens and provide novel opportunities for developing specific inhibitors targeting PaCGL.


Catalytic Domain , Cystathionine gamma-Lyase , Hydrogen Sulfide , Pseudomonas aeruginosa , Pseudomonas aeruginosa/enzymology , Cystathionine gamma-Lyase/metabolism , Cystathionine gamma-Lyase/chemistry , Crystallography, X-Ray , Substrate Specificity , Hydrogen Sulfide/metabolism , Hydrogen Sulfide/chemistry , Models, Molecular , Cysteine/metabolism , Cysteine/chemistry , Protein Conformation , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Humans , Homocysteine/metabolism , Homocysteine/chemistry , Catalysis
6.
Chemosphere ; 358: 142140, 2024 Jun.
Article En | MEDLINE | ID: mdl-38688348

Carbon-encapsulated iron oxide nanoparticles (CE-nFe) have been obtained from an industrial waste (oil mill wastewater-OMW, as a carbonaceous source), and using iron sulfate as metallic precursor. In an initial step, the hydrochar obtained has been thermally activated under an inert atmosphere at three different temperatures (600 °C, 800 °C and 1000 °C). The thermal treatment promotes the development of core-shell nanoparticles, with an inner core of α-Fe/Fe3O4, surrounded by a well-defined graphite shell. Temperatures above 800 °C are needed to promote the graphitization of the carbonaceous species, a process promoted by iron nanoparticles through the dissolution, diffusion and growth of the carbon nanostructures on the outer shell. Breakthrough column tests show that CE-nFe exhibit an exceptional performance for H2S removal with a breakthrough capacity larger than 0.5-0.6 g H2S/gcatalyst after 3 days experiment. Experimental results anticipate the crucial role of humidity and oxygen in the adsorption/catalytic performance. Compared to some commercial samples, these results constitute a three-fold increase in the catalytic performance under similar experimental conditions.


Carbon , Hydrogen Sulfide , Industrial Waste , Carbon/chemistry , Industrial Waste/analysis , Hydrogen Sulfide/chemistry , Adsorption , Catalysis , Iron/chemistry , Wastewater/chemistry , Nanoparticles/chemistry , Ferric Compounds/chemistry
7.
Int J Pharm ; 657: 124143, 2024 May 25.
Article En | MEDLINE | ID: mdl-38663641

Gastric ulcer, a significant health issue characterized by the degradation of the gastric mucosa, often arises from excessive gastric acid secretion and poses a challenge in current medical treatments due to the limited efficacy and side effects of first-line drugs. Addressing this, our study develops a novel therapeutic strategy leveraging gas therapy, specifically targeting the release of hydrogen sulfide (H2S) in the treatment of gastric ulcers. We successfully developed a composite nanoparticle, named BSA·SH-DATS, through a two-step process. Initially, bovine serum albumin (BSA) was sulfhydrated to generate BSA·SH nanoparticles via a mercaptosylation method. Subsequently, these nanoparticles were further functionalized by incorporating diallyltrisulfide (DATS) through a precise Michael addition reaction. This sequential modification resulted in the creation of BSA·SH-DATS nanoparticles. Our comprehensive in vitro and in vivo investigations demonstrate that these nanoparticles possess an exceptional ability for site-specific action on gastric mucosal cells under the controlled release of H2S in response to endogenous glutathione (GSH), markedly diminishing the production of pro-inflammatory cytokines, thereby alleviating inflammation and apoptosis. Moreover, the BSA·SH-DATS nanoparticles effectively regulate critical inflammatory proteins, including NF-κB and Caspase-3. Our study underscores their potential as a transformative approach for gastric ulcer treatment.


Allyl Compounds , Ethanol , Gastric Mucosa , Hydrogen Sulfide , Nanoparticles , Serum Albumin, Bovine , Stomach Ulcer , Sulfides , Animals , Sulfides/chemistry , Sulfides/administration & dosage , Sulfides/pharmacology , Nanoparticles/chemistry , Ethanol/chemistry , Allyl Compounds/chemistry , Allyl Compounds/pharmacology , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Gastric Mucosa/metabolism , Gastric Mucosa/drug effects , Hydrogen Sulfide/chemistry , Serum Albumin, Bovine/chemistry , Male , Apoptosis/drug effects , Glutathione/metabolism , Mice , Cytokines/metabolism , Humans , NF-kappa B/metabolism
8.
Anal Chim Acta ; 1299: 342434, 2024 Apr 22.
Article En | MEDLINE | ID: mdl-38499420

BACKGROUND: Cancer as a leading cause of premature death worldwide has become a major threat to human health due to the high incidence and mortality. Monitoring tumor markers are reliable and significantly important for early detection of cancers. In complex biological systems, it is of great urgency but still remains challenging to conceive a fluorescent probe with multiple tumor markers detection property. Hydrogen sulfide (H2S) and pH are two target biomarkers for diagnosis of early cancer. The preparation of a novel probe with H2S and pH dual detection functions is highly anticipated. RESULTS: Herein, a novel sequential detection probe HTPQ-HS for H2S and pH has been developed. In this system, HPQ (2-(2 -hydroxyphenyl)-4(3H)-quinazolinone) structure combined with triphenylamine is applied as the fluorophore, and 2, 4-dinitrophenylsulfonyl group is used as the recognition group. In the presence of H2S, HTPQ-HS is transformed into product HTPQ-OH which shows fluorescence enhancement (29-fold) at 525 nm in less than 4 min and further displays repeatable acid-base responsive ability. HTPQ-HS is able to sequentially response to H2S and pH in living cells and does not react directly with pH. Owing to the low cytotoxicity, HTPQ-HS is able to detect exogenous and endogenous H2S in colon cancer cells and mice, monitor H2S in inflammation model and in foodstuffs. As the environment changes from acidic to alkaline, the fluorescence intensity ratio (I470/I530) of product HTPQ-OH changes remarkably, illustrating the ratiometric fluorescent responsiveness to pH. SIGNIFICANCE AND NOVELTY: A multifunctional fluorescent probe HTPQ-HS for sequential detection of H2S and pH is synthesized. Probe HTPQ-OH realizes the monitoring of dynamic changes in intracellular pH and displays prospective application in security printing. We expect that our work could offer an important guidance on the development of multifunctional fluorescent probes for visualizing H2S and pH in biology and environment.


Fluorescent Dyes , Hydrogen Sulfide , Humans , Animals , Mice , Fluorescent Dyes/chemistry , Hydrogen Sulfide/chemistry , HeLa Cells , Hydrogen-Ion Concentration , Biomarkers, Tumor
9.
Chem Rev ; 124(7): 4124-4257, 2024 Apr 10.
Article En | MEDLINE | ID: mdl-38512066

Hydrogen sulfide (H2S) is not only a well-established toxic gas but also an important small molecule bioregulator in all kingdoms of life. In contemporary biology, H2S is often classified as a "gasotransmitter," meaning that it is an endogenously produced membrane permeable gas that carries out essential cellular processes. Fluorescent probes for H2S and related reactive sulfur species (RSS) detection provide an important cornerstone for investigating the multifaceted roles of these important small molecules in complex biological systems. A now common approach to develop such tools is to develop "activity-based probes" that couple a specific H2S-mediated chemical reaction to a fluorescent output. This Review covers the different types of such probes and also highlights the chemical mechanisms by which each probe type is activated by specific RSS. Common examples include reduction of oxidized nitrogen motifs, disulfide exchange, electrophilic reactions, metal precipitation, and metal coordination. In addition, we also outline complementary activity-based probes for imaging reductant-labile and sulfane sulfur species, including persulfides and polysulfides. For probes highlighted in this Review, we focus on small molecule systems with demonstrated compatibility in cellular systems or related applications. Building from breadth of reported activity-based strategies and application, we also highlight key unmet challenges and future opportunities for advancing activity-based probes for H2S and related RSS.


Hydrogen Sulfide , Hydrogen Sulfide/chemistry , Fluorescent Dyes/chemistry , Diagnostic Imaging , Sulfur , Disulfides
10.
Analyst ; 149(4): 1280-1288, 2024 Feb 12.
Article En | MEDLINE | ID: mdl-38226660

In this work, a fluorescent probe, TPABF-HS, was developed for detecting hydrogen sulfide (H2S) using a human serum albumin (HSA)-binding-based approach for amplifying the fluorescence signal and extending the linear correlation range. Compared to the most recent probes for H2S, the most interesting feature of the detection system developed herein was the especially wide linear range (0-1000 µM (0-100 eq.)), which covered the physiological and pathological levels of H2S. TPABF-HS could be used in applications high sensitivity and selectivity with an LOD value of 0.42 µM. Further, site-competition experiments and molecular docking simulation experiments indicated that signal amplification was realized by the binding of the TPABF fluorophore to the naproxen-binding site of HSA. Moreover, the extension of the measurement span could allow for applications in living cells and Caenorhabditis elegans for imaging both exogenous and endogenous H2S. This work brings new information to the strategy of signal processing by exploiting fluorescent probes.


Fluorescent Dyes , Hydrogen Sulfide , Humans , Fluorescent Dyes/toxicity , Fluorescent Dyes/chemistry , Hydrogen Sulfide/chemistry , Molecular Docking Simulation , HeLa Cells , Microscopy, Fluorescence
11.
J Environ Manage ; 351: 119784, 2024 Feb.
Article En | MEDLINE | ID: mdl-38081091

During the long-term stabilization process of landfills, the pressure field undergoes constant changes. This study constructed dynamic pressure changes scenarios of high-pressure differentials (0.6 MPa) and low-pressure differentials (0.2 MPa) in the landfill pressure field at 25 °C and 50 °C, and investigated the sulfate reduction behavior in response to landfill dynamic pressure changes. The results showed that the pressurization or depressurization of high-pressure differentials caused more significant differences in sulfate reduction behavior than that of low-pressure differentials. The lowest hydrogen sulfide (H2S) release peak concentration under pressurization was only 29.67% of that under initial pressure condition; under depressurization, the highest peak concentration of H2S was up to 21,828 mg m-3, posing a serious risk of H2S pollution. Microbial community and correlation analysis showed that pressure had a negative impact on the sulfate-reducing bacteria (SRB) community, and the SRB community adjusted its structure to adapt to pressure changes. Specific SRBs were further enriched with pressure changes. Differential H2S release behavior under pressure changes in the 25 °C pressure environments were mediated by Desulfofarcimen (ASV343) and Desulfosporosinus (ASV1336), while Candidatus Desulforudis (ASV24) and Desulfohalotomaculum (ASV94) played a key role at 50 °C. This study is helpful in the formulation of control strategies for the source of odor pollution in landfills.


Desulfovibrio , Hydrogen Sulfide , Hydrogen Sulfide/chemistry , Waste Disposal Facilities , Sulfates/chemistry
12.
Article En | MEDLINE | ID: mdl-37904284

Gaseous signaling molecules such as nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2 S) have recently been recognized as essential signal mediators that regulate diverse physiological and pathological processes in the human body. With the evolution of gaseous signaling molecule biology, their therapeutic applications have attracted growing attention. One of the challenges in translational research of gaseous signaling molecules is the lack of efficient and safe delivery systems. To tackle this issue, researchers developed a library of gas donors, which are low molecular weight compounds that can release gaseous signaling molecules upon decomposition under physiological conditions. Despite the significant efforts to control gaseous signaling molecule release from gas donors, the therapeutic potential of gaseous signaling molecules cannot be fully explored due to their unfavorable pharmacokinetics and toxic side effects. Recently, the use of nanoparticle-based gas donors, especially self-assembled polymeric gas donors, have emerged as a promising approach. In this review, we describe the development of conventional small gas donors and the challenges in their therapeutic applications. We then illustrate the concepts and critical aspects for designing self-assembled polymeric gas donors and discuss the advantages of this approach in gasotransmistter delivery. We also highlight recent efforts to develop the delivery systems for those molecules based on self-assembled polymeric nanostructures. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies.


Gases , Hydrogen Sulfide , Humans , Nanomedicine , Signal Transduction , Hydrogen Sulfide/chemistry , Carbon Monoxide/therapeutic use , Nitric Oxide , Polymers
13.
Spectrochim Acta A Mol Biomol Spectrosc ; 308: 123674, 2024 Mar 05.
Article En | MEDLINE | ID: mdl-38042125

Hydrogen sulfide (H2S) is a gas with a toxic odor that plays an irreplaceable role in physiological activities within the mammalian body. Therefore, it is important to do the distribution and quantitative detection of H2S in mammalian cells. In this paper, a fluorescence probe (EDPH) based on purine scaffold was designed and synthesized with high sensitivity and good selectivity. H2S induced ether bond breakage in EDPH, resulting in a significant redshift of the absorption band (from 370 nm to 500 nm) with a Stokes shift of 130 nm. After the addition of H2S, the fluorescence intensity of EDPH showed a good linear correlation with the concentration of H2S, which enabled the quantitative detection of H2S with a low limit of detection (41 nM). Finally, the EDPH was applied to the cellular Hele, and the probe has good cellularity imaging capability for the detection of H2S in living systems.


Fluorescent Dyes , Hydrogen Sulfide , Animals , Fluorescent Dyes/chemistry , HeLa Cells , Hydrogen Sulfide/chemistry , Mammals , Optical Imaging , Purines
14.
Small ; 20(22): e2309529, 2024 May.
Article En | MEDLINE | ID: mdl-38100303

Carbon monoxide shows great therapeutic potential in anti-cancer. In particular, the construction of multifunctional CO delivery systems can promote the precise delivery of CO and achieve ideal therapeutic effects, but there are still great challenges in design. In this work, a RSS and ROS sequentially activated CO delivery system is developed for boosting NIR imaging-guided on-demand photodynamic therapy. This designed system is composed of a CO releaser (BOD-CO) and a photosensitizer (BOD-I). BOD-CO can be specifically activated by hydrogen sulfide with simultaneous release of CO donor and NIR fluorescence that can identify H2S-rich tumors and guide light therapy, also depleting H2S in the process. Moreover, BOD-I generates 1O2 under long-wavelength light irradiation, enabling both PDT and precise local release of CO via a photooxidation mechanism. Such sequential activation of CO release by RSS and ROS ensured the safety and controllability of CO delivery, and effectively avoided leakage during delivery. Importantly, cytotoxicity and in vivo studies reveal that the release of CO combined with the depletion of endogenous H2S amplified PDT, achieving ideal anticancer results. It is believed that such theranostic nanoplatform can provide a novel strategy for the precise CO delivery and combined therapy involved in gas therapy and PDT.


Carbon Monoxide , Photochemotherapy , Reactive Oxygen Species , Photochemotherapy/methods , Carbon Monoxide/chemistry , Reactive Oxygen Species/metabolism , Humans , Animals , Cell Line, Tumor , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Mice , Infrared Rays , Hydrogen Sulfide/chemistry
15.
J Nanobiotechnology ; 21(1): 483, 2023 Dec 16.
Article En | MEDLINE | ID: mdl-38104180

Salmonellosis is a globally extensive food-borne disease, which threatens public health and results in huge economic losses in the world annually. The rising prevalence of antibiotic resistance in Salmonella poses a significant global concern, emphasizing an imperative to identify novel therapeutic agents or methodologies to effectively combat this predicament. In this study, self-assembly hydrogen sulfide (H2S)-responsive nanoprodrugs were fabricated with poly(α-lipoic acid)-polyethylene glycol grafted rhein and geraniol (PPRG), self-assembled into core-shell nanoparticles via electrostatic, hydrophilic and hydrophobic interactions, with hydrophilic exterior and hydrophobic interior. The rhein and geraniol are released from self-assembly nanoprodrugs PPRG in response to Salmonella infection, which is known to produce hydrogen sulfide (H2S). PPRG demonstrated stronger antibacterial activity against Salmonella compared with rhein or geraniol alone in vitro and in vivo. Additionally, PPRG was also able to suppress the inflammation and modulate gut microbiota homeostasis. In conclusion, the as-prepared self-assembly nanoprodrug sheds new light on the design of natural product active ingredients and provides new ideas for exploring targeted therapies for specific Enteropathogens. Graphical  illustration for construction of self-assembly nanoprodrugs PPRG and its antibacterial and anti-inflammatory activities on experimental Salmonella infection in mice.


Hydrogen Sulfide , Salmonella Infections , Animals , Mice , Salmonella typhimurium , Hydrogen Sulfide/chemistry , Salmonella Infections/drug therapy , Salmonella Infections/microbiology , Anti-Bacterial Agents/pharmacology
16.
J Am Chem Soc ; 145(46): 25486-25494, 2023 11 22.
Article En | MEDLINE | ID: mdl-37950698

Hydrogen sulfide (H2S), an endogenous signaling molecule, is known to play a pivotal role in neuroprotection, vasodilation, and hormonal regulation. To further explore the biological effects of H2S, refined donors that facilitate its biological delivery, especially under specific (patho) physiological conditions, are needed. In the present study, we demonstrate that ortho-substituted, aryl boronate esters provide two unique and distinct pathways for H2S release from thioamide-based donors: Lewis acid-facilitated hydrolysis and reactive oxygen species (ROS)-induced oxidation/cyclization. Through a detailed structure-activity relationship study, donors that resist hydrolysis and release H2S solely via the latter mechanism were identified, which have the added benefit of providing a potentially useful heterocycle as the lone byproduct of this novel chemistry. To highlight this, we developed an ROS-activated donor (QH642) that simultaneously synthesizes a benzoxazole-based fluorophore en route to its H2S delivery. A distinct advantage of this design over earlier self-reporting donors is that fluorophore formation is possible only if H2S has been discharged from the donor. This key feature eliminates the potential for false positives and provides a more accurate depiction of reaction progress and donor delivery of H2S, including in complex cellular environments.


Hydrogen Sulfide , Humans , Reactive Oxygen Species , Self Report , Hydrogen Sulfide/chemistry , Signal Transduction , Structure-Activity Relationship
17.
ACS Macro Lett ; 12(11): 1583-1588, 2023 11 21.
Article En | MEDLINE | ID: mdl-37937586

Hydrogen sulfide (H2S) is an important gaseous signaling molecule with unique pleiotropic pharmacological effects, but may be limited for clinical translation due to the lack of a reliable delivery form that delivers exogenous H2S to cells at action site with precisely controlled dosage. Herein, we report the design of a poly(thiourethane) (PTU) self-immolative polymer terminally caged with an acrylate moiety to trigger release of H2S in response to cysteine (Cys) and homocysteine (Hcy), the most used and independent indicators of neurodegenerative diseases. The synthesized PTU polymer was then coated with the red-blood-cell (RBC) membrane in the presence of solubilizing agent to self-assemble into nanoparticles with enhanced stability and cytocompatibility. The Hcy/Cys mediated addition/cyclization chemistry actuated the biomimetic polymeric nanoparticles to disintegrate into carbonyl sulfide (COS), and finally convert into H2S via the ubiquitous carbonic anhydrase (CA). H2S released in a controlled manner exhibited a strong antioxidant ability to resist Alzheimer's disease (AD)-related oxidative stress factors in BV-2 cells, a neurodegenerative disease model in vitro. Thus, this work may provide an effective strategy to construct H2S donors that can degrade in response to a specific pathological microenvironment for the treatment of neurodegenerative diseases.


Hydrogen Sulfide , Neurodegenerative Diseases , Humans , Cysteine , Hydrogen Sulfide/chemistry , Erythrocyte Membrane/metabolism , Polymers
18.
Chemistry ; 29(66): e202302197, 2023 Nov 24.
Article En | MEDLINE | ID: mdl-37665099

Stimuli-responsive fluorogenic prodrugs are advantageous for the targeted drug delivery enabling real-time non-invasive monitoring with turn-on fluorescence. We report herein the dual-stimuli (ROS and CA)-responsive thiocarbamate-based prodrug (AM-TCB) for the turn-on fluorogenic delivery of the naphthalimide-based anticancer agent amonafide along with the gasotransmitter hydrogen sulfide (H2 S). A carbamate-based prodrug AM-CB was also designed, capable of releasing the anticancer agent amonafide without any H2 S. The prodrugs were synthesized using multi-step organic synthesis. UV-Vis and fluorescence spectroscopic studies revealed selective reactivity of the boronate ester group of prodrugs towards ROS (primarily H2 O2 ) with the release of amonafide and COS/CO2 via self-immolative processes. Hydrolysis of the generated COS by carbonic anhydrase (CA) produces H2 S. While the prodrug AM-TCB retained the anticancer activity of free amonafide in cancer cells (MDA-MB-231 and HeLa), unlike amonafide, it enhanced the cellular viability of the non-malignant cells (HEK-293). Fluorescence imaging in HeLa cells revealed the simultaneous delivery of the anticancer agent and H2 S from AM-TCB with turn-on fluorescence. Western blot studies further revealed the cytoprotective effects of the released H2 S from AM-TCB. The present adjuvant strategy therefore would be helpful in future for ameliorating the anticancer drug-induced side-effects.


Antineoplastic Agents , Hydrogen Sulfide , Prodrugs , Humans , Prodrugs/pharmacology , Prodrugs/chemistry , Hydrogen Sulfide/chemistry , HeLa Cells , Fluorescence , Reactive Oxygen Species , HEK293 Cells , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry
19.
Redox Biol ; 67: 102899, 2023 11.
Article En | MEDLINE | ID: mdl-37748320

In an attempt to understand the cellular mechanisms of H2S signalling, recent research has focused on supersulfide (i.e., alkyl and inorganic hydropersulfide) formation and subsequent reactivity. While our understanding of supersulfides in biology has rapidly advanced, there are some chemical features of this unique functional group that require re-evaluation. Persulfides, such as glutathione hydropersulfide, have been called "supersulfide" as it is assumed that the alkyl hydropersulfide (RSSH) functional group is a superior nucleophile compared to the corresponding thiol (RSH) due to the alpha effect. However, recent quantum mechanical calculations and experimental data show that persulfides are not "super" nucleophiles, but rather potent electrophiles in cellular biology. It is proposed here that persulfides, via their electrophilic signalling effects, induces a cellular hormesis effect, which may explain the observed effects of altered RSSH production. Therefore, the electrophilic and thiol oxidant properties of persulfides should considered in cellular biology.


Hydrogen Sulfide , Hydrogen Sulfide/chemistry , Sulfides/chemistry , Sulfhydryl Compounds/chemistry , Signal Transduction
20.
Water Environ Res ; 95(8): e10916, 2023 Aug.
Article En | MEDLINE | ID: mdl-37533124

Granulated coal ash was prepared by mixing coal ash derived from a coal electric power plant and blast furnace cement, to remove hydrogen sulfide from aquatic environment. In this study, we investigate the effects of the composition of the coal ash used to prepare the granulated coal ash on its hydrogen sulfide removal performance. Manganese, magnesium, and calcium contents in the granulated coal ash were found to be the major factors in controlling the rate of hydrogen sulfide removal. The kinetics of hydrogen sulfide removal by the granulated coal ash were expressed as a first-order equation with a rate constant of 0.0081-0.080 h-1 . The rate constant for hydrogen sulfide removal obtained in this study correlated well with the manganese content in the granulated coal ash. The increasing surface pH attributed to the hydrolysis of calcium and magnesium on the surface of the granulated coal ash slightly increased the hydrogen sulfide removal rate. PRACTITIONER POINTS: Adsorbents for H2 S are prepared by coal ash from different coal blend and coal electric power generation processes. Adsorbents tested in this study could remove hydrogen sulfide effectively. Manganese oxide in the adsorbents enhanced the removal rate of hydrogen sulfide. Adsorbents tested in this study contribute to sustainable development goals in terms of coal fly ash recycling.


Coal Ash , Hydrogen Sulfide , Coal Ash/chemistry , Hydrogen Sulfide/chemistry , Water/chemistry , Calcium , Manganese , Magnesium , Coal
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