Acid-Triggered Degradation of Three-In-One Ag2S Quantum Dots for In Situ Ratiometric NIR-II Fluorescence Imaging-Guided Ion/Gas Combination Therapy.

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.

Hydrogen Sulfide-Induced Activatable Photodynamic Therapy Adjunct to Disruption of Subcellular Glycolysis in Cancer Cells by a Fluorescence-SERS Bimodal Iridium Metal-Organic Hybrid.

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.

An injectable hydrogel dressing for controlled release of hydrogen sulfide pleiotropically mediates the wound microenvironment.

The healing of scalded wounds faces many challenges such as chronic inflammation, oxidative stress, wound infection, and difficulties in vascular and nerve regeneration. Treating a single problem cannot effectively coordinate the complex regenerative microenvironment of scalded wounds, limiting the healing and functional recovery of the skin. Therefore, there is a need to develop a multi-effect treatment plan that can adaptively address the issues at each stage of wound healing. In this study, we propose a scheme for on-demand release of hydrogen sulfide (H2S) based on the concentration of reactive oxygen species (ROS) in the wound microenvironment. This is achieved by encapsulating peroxythiocarbamate (PTCM) in the ROS-responsive polymer poly(ethylene glycol)-poly(L-methionine) (PMet) to form nanoparticles, which are loaded into a thermosensitive injectable hydrogel, F127-poly(L-aspartic acid-N-hydroxysuccinimide) (F127-P(Asp-NHS)), to create a scald dressing. The H2S released by the hydrogel dressing on demand regulates the wound microenvironment by alleviating infection, reducing oxidative stress, and remodeling inflammation, thereby accelerating the healing of full-thickness scalded wounds. This hydrogel dressing for the adaptive release of H2S has great potential in addressing complex scalded wounds associated with infection and chronic inflammation.

An Expanded Palette of Fluorescent COS/H2S-Releasing Donors for H2S Delivery, Detection, and In Vivo Application.

Hydrogen sulfide (H2S) is an important reactive sulfur species that is involved in many biological functions, and H2S imbalances have been indicated as a potential biomarker for various diseases. Different H2S donors have been developed to deliver H2S directly to biological systems, but few reports include donors with optical responses that allow for tracking of H2S release. Moreover, donor systems that use the same chemistry to deliver H2S across a palette of fluorescent responses remain lacking. Here we report five thiol-activated fluorescence turn-on COS/H2S donors that utilize blue, yellow, orange, red, and near infrared-emitting dyes functionalized with an H2S-releasing sulfenyl thiocarbonate scaffold. Upon treatment with thiols, each donor provides a fluorescence turn-on response (3-310-fold) and high H2S release efficiencies (>60 %). Using combined electrode and fluorescence experiments, we directly correlate the measured H2S release with the fluorescence response. All donors are biocompatible and release H2S in live cell environments. In addition, we demonstrate that the NIR donor allows for imaging H2S release in live rats via subcutaneous injection of the donor loaded into an alginate gel, which to the best of our knowledge is the first in vivo tracking of H2S release from a fluorogenic donor in non-transparent organisms.

Endogenous H2S-activated Ag nanoparticles embedded in programmed DNA-cubes for specific visualization of colorectal cancer cells.

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.

Depletion and Downregulation of Hydrogen Sulfide Using an Activatable Probe for Promoting Photothermal Therapy toward Colorectal Cancers.

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.

Catalytic specificity and crystal structure of cystathionine γ-lyase from Pseudomonas aeruginosa.

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.

Exceptional performance of Fe@carbon-rich nanoparticles prepared via hydrothermal carbonization of oil mill wastes for H2S removal.

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.

Adsorption behavior of hydrogen sulfide in the channels of Li-ABW zeolite: A study using density functional theory.

H2S is a highly toxic, flammable gas that poses risks to health, the environment, and industrial infrastructure. Zeolites, with their high porosity, offer a promising solution for its removal. This study employs density functional theory (DFT) to investigate the adsorption behavior of H2S within the Li-ABW zeolite framework, focusing on the synergistic effect of co-adsorbed water molecules. Six distinct systems were modeled: empty Li-ABW zeolite, half and full filled Li-ABW with H2O or H2S molecules, and equally filled zeolite with H2S and H2O molecules. Detailed analysis of geometric, energetic, and electronic properties reveals that the presence of water significantly enhances H2S adsorption in Li-ABW. Increased bond lengths between H2S and the zeolite framework suggest possible dissociative adsorption, while weakened H2S-zeolite interaction compared to H2O-zeolite interaction indicates facile H2S desorption. Furthermore, charge transfer analysis and HOMO/LUMO plots highlight stronger interactions and a more balanced electron distribution in the co-adsorbed system. Interestingly, the presence of water minimizes structural deformations of the zeolite framework while facilitating the formation of additional hydrogen bonds, potentially further promoting H2S desorption through water extraction. These findings demonstrate that Li-ABW zeolite, particularly in conjunction with water molecules, exhibits remarkable potential for efficient and selective H2S adsorption, offering promising avenues for practical applications in gas sweetening and industrial gas purification. In order to realize this potential, further investigation into the effects of solvents and cation exchange is necessary, which are outlined for future research.

Construction of diallyltrisulfide nanoparticles for alleviation of ethanol-induced acute gastric injury.

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.

A multifunctional fluorescent probe for sequential detection of hydrogen sulfide and pH in foodstuffs, living cells and mice.

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.

Acidity of persulfides and its modulation by the protein environments in sulfide quinone oxidoreductase and thiosulfate sulfurtransferase.

Persulfides (RSSH/RSS-) participate in sulfur metabolism and are proposed to transduce hydrogen sulfide (H2S) signaling. Their biochemical properties are poorly understood. Herein, we studied the acidity and nucleophilicity of several low molecular weight persulfides using the alkylating agent, monobromobimane. The different persulfides presented similar pKa values (4.6-6.3) and pH-independent rate constants (3.2-9.0 × 103 M-1 s-1), indicating that the substituents in persulfides affect properties to a lesser extent than in thiols because of the larger distance to the outer sulfur. The persulfides had higher reactivity with monobromobimane than analogous thiols and putative thiols with the same pKa, providing evidence for the alpha effect (enhanced nucleophilicity by the presence of a contiguous atom with high electron density). Additionally, we investigated two enzymes from the human mitochondrial H2S oxidation pathway that form catalytic persulfide intermediates, sulfide quinone oxidoreductase and thiosulfate sulfurtransferase (TST, rhodanese). The pH dependence of the activities of both enzymes was measured using sulfite and/or cyanide as sulfur acceptors. The TST half-reactions were also studied by stopped-flow fluorescence spectroscopy. Both persulfidated enzymes relied on protonated groups for reaction with the acceptors. Persulfidated sulfide quinone oxidoreductase appeared to have a pKa of 7.8 ± 0.2. Persulfidated TST presented a pKa of 9.38 ± 0.04, probably due to a critical active site residue rather than the persulfide itself. The TST thiol reacted in the anionic state with thiosulfate, with an apparent pKa of 6.5 ± 0.1. Overall, our study contributes to a fundamental understanding of persulfide properties and their modulation by protein environments.

Activity-Based Fluorescent Probes for Hydrogen Sulfide and Related Reactive Sulfur Species.

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.

A human serum albumin-binding-based fluorescent probe for monitoring hydrogen sulfide and bioimaging.

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.

Sulfate reduction behavior in response to landfill dynamic pressure changes.

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.

Recent advance in self-assembled polymeric nanomedicines for gaseous signaling molecule delivery.

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.

A purine-based fluorescent probe for H2S detection and imaging of cells.

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.

RSS and ROS Sequentially Activated Carbon Monoxide Release for Boosting NIR Imaging-Guided On-Demand Photodynamic Therapy.

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.

Self-assembly of H2S-responsive nanoprodrugs based on natural rhein and geraniol for targeted therapy against Salmonella Typhimurium.

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.

Cell-Membrane Coated Self-Immolative Poly(thiourethane) for Cysteine/Homocysteine-Triggered Intracellular H2S Delivery.

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.