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In this report, a versatile method is demonstrated to create colloidal suprastructures by assembly and supramolecular interlinking of microgels using droplet-based microfluidics. The behavior of the microgels is systematically investigated to evaluate the influence of their concentration on their distribution between the continuous, the droplet phase, and the interface. At low concentrations, microgels are mainly localized at the water-oil interface whereas an excess of microgels results, following the complete coverage of the water-oil interface, in their distribution in the continuous phase. To stabilize the colloidal suprastructure, on-chip gelation is introduced by adding natural polyphenol tannic acid (TA) in the water phase. TA forms interparticle linking between the poly(N-vinylcaprolactam) (PVCL) microgels by supramolecular interactions. The combination of supramolecular interlinking with the variation of the microgel concentration in microfluidic droplets enables on-chip fabrication of defined colloidal suprastructures with morphologies ranging from colloidosomes to colloidal supraballs. The obtained supracolloidal structures exhibit a pH-responsive behavior with a disintegration at alkaline conditions within a scale of seconds. The destabilization process results from the deprotonation of phenolic groups and destruction of hydrogen bonds with PVCL chains at higher pH.
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Ulcerative colitis (UC), an immune-mediated chronic inflammatory disease, drastically impacts patients' quality of life and increases their risk of colorectal cancer worldwide. However, effective oral targeted delivery and retention of drugs in colonic lesions are still great challenges in the treatment of UC. Coacervate microdroplets, formed by liquid-liquid phase separation, are recently explored in drug delivery as the simplicity in fabrication, spontaneous enrichment on small molecules and biological macromolecules, and high drug loading capacity. Herein, in this study, a biocompatible diethylaminoethyl-dextran hydrochloride/sodium polyphenylene sulfonate coacervates, coated with eudragit S100 to improve the stability and colon targeting ability, named EU-Coac, is developed. Emodin, an active ingredient in traditional Chinese herbs proven to alleviate UC symptoms, is loaded in EU-Coac (EMO@EU-Coac) showing good stability in gastric acid and pepsin and pH-responsive release behavior. After oral administration, EMO@EU-Coac can effectively target and retain in the colon, displaying good therapeutic effects on UC treatment through attenuating inflammation and oxidative stress response, repairing colonic epithelia, as well as regulating intestinal flora balance. In short, this study provides a novel and facile coacervate microdroplet delivery system for UC treatment.
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Colitis Ulcerosa , Colon , Colitis Ulcerosa/tratamiento farmacológico , Concentración de Iones de Hidrógeno , Colon/patología , Colon/metabolismo , Colon/efectos de los fármacos , Animales , Sistemas de Liberación de Medicamentos/métodos , Ácidos Polimetacrílicos/química , Ratones , Humanos , MasculinoRESUMEN
Despite significant advancements, current self-healing materials often suffer from a compromise between mechanical robustness and functional performance, particularly in terms of conductivity and responsiveness to environmental stimuli. Addressing this issue, the research introduces a self-healable and conductive copolymer, poly(ionic liquid-co-acrylic acid) (PIL-co-PAA), synthesized through free radical polymerization, and further optimized by incorporating thermoplastic polyurethane (TPU). This combination leverages the unique properties of each component, especially ion-dipole interactions and hydrogen bonds, resulting in a material that exhibits exceptional self-healing abilities and demonstrates enhanced mechanical properties and electrical conductivity. Moreover, the PIL-co-PAA/TPU films showcase alkaline-responsive behavior, a feature that broadens their applicability in dynamic environments. Through systematic characterization, including thermogravimetric analysis, tensile testing, and electrical properties measurements, the mechanisms behind the improved performance and functionality of these films are elucidated. The conductivities and ultimate tensile strength (σuts) of the PIL-co-PAA/TPU films regain 80% under 8 h healing process. To extend the applications for wearable devices, the self-healing properties of commercial cotton fabrics coated with the self-healable PIL-co-PAA are also investigated, demonstrating both self-healing and electrical properties. This study advances the understanding of self-healable conductive polymers and opens new avenues for their application in wearable technology.
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Atherosclerosis is the primary cause of cardiovascular events such as heart attacks and strokes. However, current medical practice lacks non-invasive, reliable approaches for both imaging atherosclerotic plaques and delivering therapeutic agents directly therein. Here, a biocompatible and biodegradable pH-responsive nanoscale coordination polymers (NCPs) based theranostic system is reported for managing atherosclerosis. NCPs are synthesized with a pH-responsive benzoic-imine (BI) linker and Gd3+. Simvastatin (ST), a statin not used for lowering blood cholesterol but known for its anti-inflammatory and antioxidant effects in mice, is chosen as the model drug. By incorporating ST into the hydrophobic domain of a lipid bilayer shell on NCPs surfaces, ST/NCP-PEG nanoparticles are created that are designed for dual purposes: they diagnose and treat atherosclerosis. When administered intravenously, they target atherosclerotic plaques, breaking down in the mild acidic microenvironment of the plaque to release ST, which reduces inflammation and oxidative stress, and Gd-complexes for MR imaging of the plaques. ST/NCP-PEG nanoparticles show efficacy in slowing the progression of atherosclerosis in live models and allow for simultaneous in vivo monitoring without observed toxicity in major organs. This positions ST/NCP-PEG nanoparticles as a promising strategy for the spontaneous diagnosis and treatment of atherosclerosis.
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Engineering bioactive iminosugars with pH-responsive groups is an emerging approach to develop pharmacological chaperones (PCs) able to improve lysosomal trafficking and enzymatic activity rescue of mutated enzymes. The use of inexpensive l-malic acid allowed introduction of orthoester units into the lipophilic chain of an enantiomerically pure iminosugar affording only two diastereoisomers contrary to previous related studies. The iminosugar was prepared stereoselectively from the chiral pool (d-mannose) and chosen as the lead bioactive compound, to develop novel candidates for restoring the lysosomal enzyme glucocerebrosidase (GCase) activity. The stability of orthoester-appended iminosugars was studied by 1 Hâ NMR spectroscopy both in neutral and acidic environments, and the loss of inhibitory activity with time in acid medium was demonstrated on cell lysates. Moreover, the ability to rescue GCase activity in the lysosomes as the result of a chaperoning effect was explored. A remarkable pharmacological chaperone activity was measured in fibroblasts hosting the homozygous L444P/L444P mutation, a cell line resistant to most PCs, besides the more commonly responding N370S mutation.
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Enfermedad de Gaucher , Glucosilceramidasa , Humanos , Enfermedad de Gaucher/tratamiento farmacológico , Enfermedad de Gaucher/genética , Piperidinas/farmacología , Piperidinas/metabolismo , Mutación , Fibroblastos , Concentración de Iones de HidrógenoRESUMEN
A multifunctional polydopamine/mesoporous silica nanoparticles loaded cryptotanshinone (PDA/MSN@CTS) was synthesized and subjected to investigating its physicochemical properties and anti-gastric cancer (GC) effects. Utilizing network pharmacology and molecular docking techniques, CTS was identified as our final research target. The structural morphology and physicochemical properties of PDA/MSN@CTS were examined. Near-infrared (NIR) laser was employed to evaluate the photothermal properties of the PDA/MSN@CTS, along with pH-responsive and NIR-triggered release assessments. In vitro experiments evaluated the impact of PDA/MSN@CTS on the malignant behavior of AGS gastric cells. A subcutaneous tumor model was further established to evaluate the in vivo safety of PDA/MSN@CTS. Furthermore, the in vivo photothermal efficacy of PDA/MSN@CTS, in addition to its combined effect with photothermal therapy (PTT), was investigated. Uniform and stable PDA/MSN@CTS had been successfully synthesized and demonstrated efficient release under tumor environment and NIR irradiation. Upon increasing NIR laser conditions, in vivo cytotoxicity, apoptosis rate, reactive oxygen species scavenging ability, and suppression of migration and invasion of AGS cells by PDA/MSN@CTS were significantly enhanced. In vivo assessments revealed excellent blood compatibility and biosafety of PDA/MSN@CTS, alongside robust tumor tissue targeting. Combining nanoparticles with PTT facilitated the anti-GC effects of PDA/MSN@CTS. Compared to free drugs, PDA/MSN@CTS exhibits higher selectivity towards cancer cells, demonstrating effective anticancer activity and biocompatibility both in vitro and in vivo. Furthermore, our nanomaterial possesses excellent photothermal properties, and under NIR conditions, PDA/MSN@CTS exhibits synergistic therapeutic effects.
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A unique approach is imperative for the development of drugs aimed at inhibiting various stages of infection, rather than solely focusing on bacterial viability. Among the array of unconventional targets explored for formulating novel antimicrobial medications, blocking the quorum-sensing (QS) system emerges as a highly effective and promising strategy against a variety of pathogenic microbes. In this investigation, we have successfully assessed nine α-aminoamides for their anti-QS activity using Agrobacterium tumefaciensNT1 as a biosensor strain. Among these compounds, three (2, 3and, 4) have been identified as potential anti-QS candidates. Molecular docking studies have further reinforced these findings, indicating that these compounds exhibit favorable pharmacokinetic profiles. Additionally, we have assessed the ligand's stability within the protein's binding pocket using molecular dynamics (MD) simulations and MMGBSA analysis. Further, combination of antiquorum sensing properties with antibiotics viaself-assembly represents a promising approach to enhance antibacterial efficacy, overcome resistance, and mitigate the virulence of bacterial pathogens. The release study also reflects a slow and gradual release of the metronidazole at both pH 6.5 and pH 7.4, avoiding the peaks and troughs associated with more immediate release formulations.
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Agrobacterium tumefaciens , Antibacterianos , Metronidazol , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Percepción de Quorum , Agrobacterium tumefaciens/efectos de los fármacos , Percepción de Quorum/efectos de los fármacos , Metronidazol/farmacología , Metronidazol/química , Antibacterianos/farmacología , Antibacterianos/química , Pruebas de Sensibilidad Microbiana , Geles/química , Sinergismo Farmacológico , Liberación de FármacosRESUMEN
Stimuli-responsive peptides, particularly pH-responsive variants, hold significant promise in biomedical and technological applications by leveraging the broad pH spectrum inherent to biological environments. However, the limited number of natural pH-responsive amino acids within biologically relevant pH ranges presents challenges for designing rational pH-responsive peptide assemblies. In our study, we introduce a novel approach by incorporating a library of non-natural amino acids featuring chemically diverse tertiary amine side chains. Hydrophobic and ionic properties of these non-natural amino acids facilitate their incorporation into the assembly domain when uncharged, and electrostatic repulsion promotes disassembly under lower pH conditions. Furthermore, we observed a direct relationship between the number of substitutions and the hydrophobicity of these amino acids, influencing their pH-responsive properties and enabling rational design based on desired transitional pH ranges. The structure-activity relationship of these pH-responsive peptides was evaluated by assessing their antimicrobial properties, as their antimicrobial activity is triggered by the disassembly of peptides to release active monomers. This approach not only enhances the specificity and controllability of pH responsiveness but also broadens the scope of peptide materials in biomedical and technological applications.
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The chemically triggered reversible switching of pH-responsive hydrazones involves rotary motion-induced configurational changes, serving as a prototype for constructing an array of molecular machines. Typically, the configurational isomerization of such switches into two distinct forms (E/Z) occurs through the alteration of the pH the medium, achieved by successive additions of acid and base stimuli. However, this process results in intermittent operation due to the concomitant accumulation of salt after each cycle, limiting switching performance to only a few cycles (5-6). In this context, we introduce a novel strategy for the autonomous E/Z isomerization of hydrazones in acetonitrile using pulses of trichloroacetic acid as a chemical fuel. The use of this transient acid enabled reversible switching of hydrazones even after 50â cycles without causing significant fatigue. To test the broad viability of the fuel, a series of ortho/para-substituted hydrazones were synthesized and their switching performance was investigated. The analysis of kinetic data showed a strong dependency of switching operations including the lifetime of transient state, on the electronic properties of substituents. Finally, a distinct color change from yellow to orange due to reversible switching of the para-methoxy substituted hydrazone was employed for the creation of rewritable messages on commercially available paper.
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Homopolymers of poly[N-(2-(diethylamino)ethyl) acrylamide] exhibit the ability to adsorb onto the surface of preformed or growing gold nanoparticles. The resulting hybrid materials possess a pH and thermo-sensitive nature. Consequently, their optical properties can be modulated by manipulating either the temperature or the pH. Moreover, introducing monomers based on poly(N-isopropyl acrylamide) into block or random statistical polymers enables further modulation of the thermosensitive properties. These copolymers, employed for the in-situ synthesis and/or stabilization of gold nanoparticles, lead to hybrid materials whose properties and/or particle size depend on the polymer composition and microstructure: statistical polymers emerge as superior stabilizing agents compared to their block counterparts at a constant composition.
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Currently, there is an inherent contradiction between the multifunctionality and excellent biocompatibility of anticancer drug nanocarriers, which limits their application. Therefore, to overcome this limitation, we aimed to develop a biocompatible drug delivery system for the treatment of hepatocellular carcinoma (HCC). In this study, we employed poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) as the fundamental framework of the nanocarrier and utilized the emulsion solvent evaporation method to fabricate nanoparticles loaded with paclitaxel (PTX), known as PTX-PHBV NPs. To enhance the tumor-targeting capability, a dopamine self-polymerization strategy was employed to form a pH-sensitive coating on the surface of the nanoparticles. Then, folic acid (FA)-targeting HCC was conjugated to the nanoparticles with a polydopamine (PDA) coating by using the Michael addition reaction, resulting in the formation of HCC-targeted nanoparticles (PTX-PHBV@PDA-FA NPs). The PTX-PHBV@PDA-FA NPs were characterized and analyzed by using dynamic light scattering, scanning electron microscopy, fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. Encouragingly, PTX-PHBV@PDA-FA NPs exhibited remarkable anticancer efficacy in an HCC xenograft mouse model. Furthermore, compared to raw PTX, PTX-PHBV@PDA-FA NPs showed less toxicity in vivo. In conclusion, these results demonstrate the potential of PTX-PHBV@PDA-FA NPs for HCC treatment and biocompatibility.
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Carcinoma Hepatocelular , Indoles , Neoplasias Hepáticas , Nanopartículas , Polihidroxibutiratos , Polímeros , Humanos , Animales , Ratones , Paclitaxel/uso terapéutico , Paclitaxel/química , Carcinoma Hepatocelular/tratamiento farmacológico , Ácido Fólico/química , Neoplasias Hepáticas/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Poliésteres/química , Nanopartículas/química , Concentración de Iones de Hidrógeno , Línea Celular Tumoral , Portadores de Fármacos/químicaRESUMEN
Aside from their fluorescence sensing capabilities, carbon dots doped with heteroatoms show tremendous promise as nanocarriers for medicinal compounds and as antioxidants. We present a method for producing carbon dots from chitosan and lemon extract (CLCDs) using a one-step hydrothermal coupling synthesis. The as-synthesized CLCDs exhibited remarkable colloidal stability, antioxidant behavior, cytocompatibility, and nanocarrier for drug molecules. The nanoparticles was analyzed using advanced techniques such as Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), fluorescence spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, and transmission electron microscopy (TEM) to determine the precise composition of their surface. In order to evaluate the drug transport properties of CLCDs, their surfaces were further modified with anticancer drug compounds. The drug release behavior was studied against physiologically simulated fluids and at different pH environments showing better delayed response in acidic condition. The plausible mechanistic pathways have been confirmed after fitting the results into Higuchi, Weibull and Korsmeyer-Peppas models. The goodness of fit was more than 95% for the Korsmeyer-Peppas model, with the release mechanism supported by anomalous transport. Moreover, the radical scavenging activity of CLCDs was also confirmed at low levels (1 mg/mL) which could be inferred > 85% efficacy against mostly employed testing agents (DPPH, ABTS, and hydroxyl radicals). Thus, the prepared CLCDs could be used as suitable nanovector in payload delivery with prominent antioxidant activity and low toxicity against living cell lines.
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Wound healing in movable parts, including the joints and neck, remains a critical challenge due to frequent motions and poor flexibility of dressings, which may lead to mismatching of mechanical properties and poor fitting between dressings and wounds; thus, increasing the risk of bacterial infection. This study proposes a sprayable zwitterionic antibacterial hydrogel with outstanding flexibility and desirable adhesion. This hydrogel precursor is fabricated by combining zwitterionic sulfobetaine methacrylate (SBMA) with poly(sulfobetaine methacrylate-co-dopamine methacrylamide)-modified silver nanoparticles (PSBDA@AgNPs) through robust electrostatic interactions. About 150 s of exposure to UV light, the SBMA monomer polymerizes to form PSB chains entangled with PSBDA@AgNPs, transformed into a stable and adhesion PSB-PSB@Ag hydrogel at the wound site. The resulting hydrogel has adhesive strength (15-38 kPa), large tensile strain (>400%), suitable shape adaptation, and excellent mechanical resilience. Moreover, the hydrogel displays pH-responsive behavior; the acidic microenvironment at the infected wound sites prompts the hydrogel to rapidly release AgNPs and kill bacteria. Further, the healing effect of the hydrogel is demonstrated on the rat neck skin wound, showing improved wound closing rate due to reduced inflammation and enhanced angiogenesis. Overall, the sprayable zwitterionic antibacterial hydrogel has significant potential to promote joint skin wound healing.
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Antibacterianos , Hidrogeles , Nanopartículas del Metal , Metacrilatos , Plata , Cicatrización de Heridas , Hidrogeles/química , Hidrogeles/farmacología , Hidrogeles/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Plata/química , Plata/farmacología , Ratas , Nanopartículas del Metal/química , Metacrilatos/química , Metacrilatos/farmacología , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad MicrobianaRESUMEN
A dual zwitterionic diblock copolymer (M100C100) consisting of poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC, M) and poly(3-((2-(methacryloyloxy)ethyl) dimethylammonio) propionate) (PCBMA, C) is synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. A double hydrophilic diblock copolymer (M100S100) consist of PMPC and anionic poly(3-sulfopropyl methacrylate potassium salt) (PMPS, S) is synthesized via RAFT. The degrees of polymerization of each block are 100. The charges of PMPC are neutralized intramolecularly. At neutral pH, the charges in PCBMA are also neutralized intramolecularly due to its carboxybetaine structure. Under acidic conditions, PCBMA exhibits polycation behavior as the pendant carboxy groups become protonated, forming cationic tertiary amine groups. PMPS shows permanent anionic nature independent of pH. Charge neutralized mixture of cationic M100C100 and anionic M100S100 in acidic aqueous solution forms water-soluble polyion complex (PIC) micelle owing to electrostatic attractive interactions. The core is composed of the cationic PCBMA and anionic PMPS blocks, with the PMPC blocks serving as shells that covered the core surface, forming spherical core-shell PIC micelles. Above pH 4 the pendant carboxy groups in PCBMA undergo deprotonation, transitioning to a zwitterionic state, thereby eliminating the cationic charge in PCBMA. Therefore, above pH 4 the PIC micelles are dissociated due to the disappearance of the charge interactions.
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To address the limitations of traditional photothermal therapy (PTT)/ photodynamic therapy (PDT) and real-time cancer metastasis detection, a pH-responsive nanoplatform (NP) with dual-modality imaging capability was rationally designed. Herein, 1 H,1 H-undecafluorohexylamine (PFC), served as both an oxygen carrier and a 19F magnetic resonance imaging (MRI) probe, and photosensitizer indocyanine green (ICG) were grafted onto the pH-responsive peptide hexahistidine (H6) to form H6-PFC-ICG (HPI). Subsequently, the heat shock protein 90 inhibitor, gambogic acid (GA), was incorporated into hyaluronic acid (HA) modified HPI (HHPI), yielding the ultimate HHPI@GA NPs. Upon self-assembly, HHPI@GA NPs passively accumulated in tumor tissues, facilitating oxygen release and HA-mediated cell uptake. Once phagocytosed by lysosomes, protonation of H6 was triggered due to the low pH, resulting in the release of GA. With near-infrared laser irradiation, GA-mediated decreased HSP90 expression and PFC-mediated increased ROS generation amplified the PTT/PDT effect of HHPI@GA, leading to excellent in vitro and in vivo anticancer efficacies. Additionally, the fluorescence and 19F MRI dual-imaging capabilities of HHPI@GA NPs enabled effective real-time primary cancer and lung metastasis monitoring. This work offers a novel approach for enhanced cancer phototherapy, as well as precise cancer diagnosis.
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Neoplasias Pulmonares , Nanopartículas , Fotoquimioterapia , Humanos , Fototerapia/métodos , Verde de Indocianina , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/terapia , Oxígeno , Concentración de Iones de Hidrógeno , Línea Celular TumoralRESUMEN
A microextraction based on pH-responsive deep eutectic solvent combined with high-performance liquid chromatography was developed for the separation, preconcentration, and determination of bisphenol A in water samples. Five deep eutectic solvents were prepared using thymol (hydrogen bond acceptor) and 6-, 8-, 9-, 10-, and 12-carbon carboxylic acids (hydrogen bond donor), and were used as extraction solvent. Herein, by alkalinizing the environment, phase transition takes place, and by adding acid, phase separation and extraction of analytes occur simultaneously. Some important parameters on the extraction such as deep eutectic solvent type, molar ratio of deep eutectic solvent components, deep eutectic solvent volume, potassium hydroxide concentration, hydrochloric acid volume, extraction time, and salt addition were optimized. Under the optimum conditions, intra- and interday precisions of the method based on seven replicate measurements of 10 µg L-1 of bisphenol A in water samples were 2.2% and 4.3%, respectively. The analytical performance of the method showed linearity over the concentration of 0.05-50 µg L-1 with the detection limit of 0.02 µg L-1 . The accuracy of the method was confirmed by spiking different concentrations of bisphenol A in real water samples and obtaining relative recoveries in the range of 92.5%-105.2%.
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Corroles provide a remarkable opportunity for the development of cancer theranostic agents among other porphyrinoids. While most transition metal corrole complexes are only therapeutic, post-transition metallocorroles also find their applications in bioimaging. Moreover, corroles exhibit excellent photo-physicochemical properties, which can be harnessed for antitumor and antimicrobial interventions. Nevertheless, these intriguing, yet distinct properties of corroles, have not attained sufficient momentum in cancer research. The current review provides a comprehensive summary of various cancer-relevant features of corroles ranging from their structural and photophysical properties, chelation, protein/corrole interactions, to DNA intercalation. Another aspect of the paper deals with the studies of corroles conducted in vitro and in vivo with an emphasis on medical imaging (optical and magnetic resonance), photo/sonodynamic therapies, and photodynamic inactivation. Special attention is also given to a most recent finding that shows the development of pH-responsive phosphorus corrole as a potent antitumor drug for organelle selective antitumor cytotoxicity in preclinical studies. Another biomedical application of corroles is also highlighted, signifying the application of water-soluble and completely lipophilic corroles in the photodynamic inactivation of microorganisms. We strongly believe that future studies will offer a greater possibility of utilizing advanced corroles for selective tumor targeting and antitumor cytotoxicity. In the line with future developments, an ideal pipeline is envisioned on grounds of cancer targeting nanoparticle systems upon decoration with tumor-specific ligands. Hence, we envision that a bright future lies ahead of corrole anticancer research and therapeutics.
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Antineoplásicos , Complejos de Coordinación , Neoplasias , Porfirinas , Humanos , Porfirinas/farmacología , Porfirinas/química , Porfirinas/uso terapéutico , Complejos de Coordinación/farmacología , Complejos de Coordinación/uso terapéutico , Neoplasias/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéuticoRESUMEN
Microencapsulated enzymes have been found to effectively accelerate cheese ripening. However, microencapsulated enzyme release is difficult to control, often resulting in enzyme release during cheese processing and causing texture and flavor defects. This study aims to address this issue by developing aminopeptidase-loaded pH-responsive chitosan microspheres (A-CM) for precise enzyme release during cheese ripening. An aminopeptidase with an isoelectric point (pH 5.4) close to the pH value of cheese ripening was loaded on chitosan microspheres through electrostatic interaction. Turbidity titration measurements revealed that pH 6.5 was optimal for binding aminopeptidase and microspheres, affording the highest loading efficiency of 58.16%. Various characterization techniques, including scanning electron microscopy, energy-dispersive X-ray spectroscopy, and Fourier-transform infrared spectroscopy confirmed the successful loading of aminopeptidase molecules on the chitosan microspheres. In vitro release experiments conducted during simulated cheese production demonstrated that aminopeptidase release from A-CM was pH responsive. The microspheres retained the enzyme during the coagulation and cheddaring processes (pH 5.5-6.5) and only released it after entering the cheese-ripening stage (pH 5.0-5.5). By loading aminopeptidase on chitosan microspheres, the loss rate of the enzyme in cheese whey was reduced by approximately 79%. Furthermore, compared with cheese without aminopeptidase and cheese with aminopeptidase added directly, the cheeses made with A-CM exhibited the highest proteolysis level and received superior sensory ratings for taste and smell. The content of key aroma substances, such as 2/3-methylbutanal and ethyl butyrate, in cheese with A-CM was more than 15 times higher than the others. This study provides an approach for accelerating cheese ripening through the use of microencapsulated enzymes.
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Aminopeptidasas , Queso , Quitosano , Microesferas , Quitosano/química , Concentración de Iones de Hidrógeno , Aminopeptidasas/metabolismo , Animales , Manipulación de AlimentosRESUMEN
The present study intended to develop a pH-responsive hydrogel based on Neem gum (Ng) to improve Lansoprazole (LSP) oral bioavailability. pH-responsive hydrogel formulations (F1-F9) were prepared using different Ng ratios, Acrylamide (AAm), and methylene-bis-acrylamide (MBA). The formulated hydrogels were characterized through FTIR, thermal analysis, swelling ratio, SEM, sol-gel ratios, In-Vitro drug release, and cytotoxicity analysis. Azadirachta Indica was extracted to produce a powder containing 21.5 % Ng. Prepared hydrogels showed maximum swelling at pH 7.4, whereas the swelling at an acidic pH was insignificant. LSP-loaded hydrogel demonstrated a regulated release of LSP for up to 24 h and indicated a Super Case II transport release mechanism. During the cytotoxic evaluation, the delivery system showed minimal cytotoxicity towards normal cells, while percent cytotoxicity was carried out for a longer duration (up to 96 h). The present study revealed Azadirachta indica gum-based pH-responsive hydrogel as a promising technique for precisely delivering LSP.
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Sophisticated dynamic molecular systems with diverse functions have been fabricated by using the fundamental tool of toehold-mediated strand displacement (TMSD) in the field of dynamic DNA nanotechnology. However, simple approaches to reset these TMSD-based dynamic systems are lacking due to the difficulty in creating kinetically favored pathways to implement the backward resetting reactions. Here, we develop a facile proton-driven strategy to achieve complete resetting of a modular DNA circuit by integrating a pH-responsive intermolecular CG-C+ triplex DNA and an i-motif DNA into the conventional DNA substrate. The pH-programmed strategy allows modular DNA components to specifically associate/dissociate to promote the forward/backward TMSD reactions, thereby enabling the modular DNA circuit to be repeatedly operated at a constant temperature without generating any DNA waste products. Leveraging this tractable approach, we further constructed two resettable DNA logic gates used for logical computation and two resettable catalytic DNA systems with good performance in signal transduction and amplification.