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1.
ACS Appl Mater Interfaces ; 16(24): 30980-30996, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38857433

ABSTRACT

Understanding of the interactions between macrophages and multifunctional nanoparticles is important for development of novel macrophage-based immunotherapies. Here, we investigated the effects of fluorescent thiol-organosilica particle size and surface properties on cell-particle interactions, including mitochondrial activity, using the mouse macrophage cell line J774A.1. Three different sizes of thiol-organosilica particles (150, 400, and 680 nm in diameter) containing fluorescein (OS/F150, OS/F400, and OS/F680) and particles surface functionalized with polyethylenimine (PEI) (OS/F150PEI, OS/F400PEI, and OS/F680PEI) were prepared. Flow cytometric analysis, time-lapse imaging, and single-cell analysis of particle uptake and mitochondrial activity of J774A.1 cells demonstrated variations in uptake and kinetics depending on the particle size and surface as well as on each individual cell. Cells treated with OS/F150 and OS/F150PEI showed higher uptake and mitochondrial activity than those treated with other particles. The interaction between endosomes and mitochondria was observed using 3D fluorescent imaging and was characterized by the involvement of iron transport into mitochondria by iron-containing proteins adsorbed on the particle surface. Scanning electron microscopy of the cells treated with the particles revealed alterations in cell membrane morphology, depending on particle size and surface. We performed correlative light and electron microscopy combined with time-lapse and 3D imaging to develop an integrated correlation analysis of particle uptake, mitochondrial activity, and cell membrane morphology in single macrophages. These cell-specific characteristics of macrophages against functional particles and their evaluation methods are crucial for understanding the immunological functions of individual macrophages and developing novel immunotherapies.


Subject(s)
Macrophages , Mitochondria , Organosilicon Compounds , Particle Size , Surface Properties , Mice , Animals , Mitochondria/metabolism , Macrophages/metabolism , Macrophages/cytology , Organosilicon Compounds/chemistry , Organosilicon Compounds/pharmacology , Cell Line , Polyethyleneimine/chemistry , Nanoparticles/chemistry
2.
Biosensors (Basel) ; 14(6)2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38920592

ABSTRACT

The scope of this study was to apply advances in materials science, specifically the use of organosilicate nanoparticles as a high surface area platform for passive sampling of chemicals or pre-concentration for active sensing in multiple-phase complex environmental media. We have developed a novel nanoporous organosilicate (NPO) film as an extraction phase and proof of concept for application in adsorbing hydrophobic compounds in water and sediment. We characterized the NPO film properties and provided optimization for synthesis and coatings in order to apply the technology in environmental media. NPO films in this study had a very high surface area, up to 1325 m2/g due to the high level of mesoporosity in the film. The potential application of the NPO film as a sorbent phase for sensors or passive samplers was evaluated using a model hydrophobic chemical, polychlorinated biphenyls (PCB), in water and sediment. Sorption of PCB to this porous high surface area nanoparticle platform was highly correlated with the bioavailable fraction of PCB measured using whole sediment chemistry, porewater chemistry determined by solid-phase microextraction fiber methods, and the Lumbriculus variegatus bioaccumulation bioassay. The surface-modified NPO films in this study were found to highly sorb chemicals with a log octanol-water partition coefficient (Kow) greater than four; however, surface modification of these particles would be required for application to other chemicals.


Subject(s)
Geologic Sediments , Hydrophobic and Hydrophilic Interactions , Nanoparticles , Nanoparticles/chemistry , Water/chemistry , Polychlorinated Biphenyls/analysis , Water Pollutants, Chemical/analysis , Organosilicon Compounds/chemistry , Adsorption , Surface Properties
3.
Chem Pharm Bull (Tokyo) ; 72(5): 487-497, 2024.
Article in English | MEDLINE | ID: mdl-38777760

ABSTRACT

Herein, we report the functionalization of polyhedral oligosilsesquioxanes (POSS) and related siloxanes with arynes. Using o-triazenylarylboronic acids as aryne precursors and silica gel as the activator, the transformation of siloxane bearing various arynophilic moieties on the side chains was achieved with high yields without touching the siloxane core. This method was applied to the conjugation of POSS and pharmaceutical cores using an aryne derived from the synthetic intermediate of cabozantinib. Furthermore, orthogonal dual functionalization of POSS was realized by combining the aryne reaction with Huisgen cyclization.


Subject(s)
Alkynes , Boronic Acids , Siloxanes , Alkynes/chemistry , Boronic Acids/chemistry , Cyclization , Molecular Structure , Organosilicon Compounds/chemistry , Organosilicon Compounds/chemical synthesis , Siloxanes/chemistry , Triazines/chemistry
4.
ACS Nano ; 18(20): 13333-13345, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38717602

ABSTRACT

A persistent inflammatory response, intrinsic limitations in axonal regenerative capacity, and widespread presence of extrinsic axonal inhibitors impede the restoration of motor function after a spinal cord injury (SCI). A versatile treatment platform is urgently needed to address diverse clinical manifestations of SCI. Herein, we present a multifunctional nanoplatform with anisotropic bimodal mesopores for effective neural circuit reconstruction after SCI. The hierarchical nanoplatform features of a Janus structure consist of dual compartments of hydrophilic mesoporous silica (mSiO2) and hydrophobic periodic mesoporous organosilica (PMO), each possessing distinct pore sizes of 12 and 3 nm, respectively. Unlike traditional hierarchical mesoporous nanomaterials with dual-mesopores interlaced with each other, the two sets of mesopores in this Janus nanoplatform are spatially independent and possess completely distinct chemical properties. The Janus mesopores facilitate controllable codelivery of dual drugs with distinct properties: the hydrophilic macromolecular enoxaparin (ENO) and the hydrophobic small molecular paclitaxel (PTX). Anchoring with CeO2, the resulting mSiO2&PMO-CeO2-PTX&ENO nanoformulation not only effectively alleviates ROS-induced neuronal apoptosis but also enhances microtubule stability to promote intrinsic axonal regeneration and facilitates axonal extension by diminishing the inhibitory effect of extracellular chondroitin sulfate proteoglycans. We believe that this functional dual-mesoporous nanoplatform holds significant potential for combination therapy in treating severe multifaceted diseases.


Subject(s)
Spinal Cord Injuries , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/physiopathology , Animals , Porosity , Silicon Dioxide/chemistry , Paclitaxel/pharmacology , Paclitaxel/chemistry , Anisotropy , Nerve Regeneration/drug effects , Hydrophobic and Hydrophilic Interactions , Apoptosis/drug effects , Rats , Nanostructures/chemistry , Mice , Particle Size , Organosilicon Compounds/chemistry , Organosilicon Compounds/pharmacology
5.
J Nanobiotechnology ; 22(1): 249, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38745193

ABSTRACT

BACKGROUND: Chemotherapy, the mainstay treatment for metastatic cancer, presents serious side effects due to off-target exposure. In addition to the negative impact on patients' quality of life, side effects limit the dose that can be administered and thus the efficacy of the drug. Encapsulation of chemotherapeutic drugs in nanocarriers is a promising strategy to mitigate these issues. However, avoiding premature drug release from the nanocarriers and selectively targeting the tumour remains a challenge. RESULTS: In this study, we present a pioneering method for drug integration into nanoparticles known as mesoporous organosilica drugs (MODs), a distinctive variant of periodic mesoporous organosilica nanoparticles (PMOs) in which the drug is an inherent component of the silica nanoparticle structure. This groundbreaking approach involves the chemical modification of drugs to produce bis-organosilane prodrugs, which act as silica precursors for MOD synthesis. Mitoxantrone (MTO), a drug used to treat metastatic breast cancer, was selected for the development of MTO@MOD nanomedicines, which demonstrated a significant reduction in breast cancer cell viability. Several MODs with different amounts of MTO were synthesised and found to be efficient nanoplatforms for the sustained delivery of MTO after biodegradation. In addition, Fe3O4 NPs were incorporated into the MODs to generate magnetic MODs to actively target the tumour and further enhance drug efficacy. Importantly, magnetic MTO@MODs underwent a Fenton reaction, which increased cancer cell death twofold compared to non-magnetic MODs. CONCLUSIONS: A new PMO-based material, MOD nanomedicines, was synthesised using the chemotherapeutic drug MTO as a silica precursor. MTO@MOD nanomedicines demonstrated their efficacy in significantly reducing the viability of breast cancer cells. In addition, we incorporated Fe3O4 into MODs to generate magnetic MODs for active tumour targeting and enhanced drug efficacy by ROS generation. These findings pave the way for the designing of silica-based multitherapeutic nanomedicines for cancer treatment with improved drug delivery, reduced side effects and enhanced efficacy.


Subject(s)
Antineoplastic Agents , Breast Neoplasms , Cell Survival , Mitoxantrone , Organosilicon Compounds , Humans , Breast Neoplasms/drug therapy , Female , Cell Survival/drug effects , Organosilicon Compounds/chemistry , Organosilicon Compounds/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Mitoxantrone/pharmacology , Mitoxantrone/chemistry , Mitoxantrone/therapeutic use , Cell Line, Tumor , Drug Carriers/chemistry , Silicon Dioxide/chemistry , Porosity , Drug Liberation , Nanoparticles/chemistry , MCF-7 Cells , Nanomedicine/methods , Reactive Oxygen Species/metabolism
6.
Int J Biol Macromol ; 271(Pt 1): 132542, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38801848

ABSTRACT

In this research, poly-chloropropylmethyl-silsesquioxanen was prepared and decorated with ZIF-8 in order to investigate its loading capacity for acyclovir and tetracycline. Before and after drug loadings, the composites were characterized by FT-IR, SEM-EDS, XRD, and XPS analyses. Then, the in-vitro release of these drugs was investigated by UV-Vis spectroscopy in different buffers (pH = 5, 7.4, and 9.1). The results showed that the release of ACV reached a maximum amount of 41.3 mg at pH = 7.4 during 12 h. In comparison, the release of TC reached a maximum amount of 22.5 mg at pH = 5 during 6 h. The blood compatibility, in-vitro cytotoxicity on the L929 fibroblast cells line, and antibacterial assay against Staphylococcus aureus and Pseudomonas aeruginosa were also investigated for this composite as a drug carrier.


Subject(s)
Acyclovir , Anti-Bacterial Agents , Tetracycline , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Acyclovir/chemistry , Acyclovir/pharmacology , Hydrogen-Ion Concentration , Tetracycline/chemistry , Tetracycline/pharmacology , Animals , Mice , Staphylococcus aureus/drug effects , Drug Liberation , Drug Carriers/chemistry , Organosilicon Compounds/chemistry , Cell Line , Humans , Pseudomonas aeruginosa/drug effects
7.
Int J Biol Macromol ; 271(Pt 2): 132345, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38750848

ABSTRACT

As an important source of green cleaning flame retardants, bio-based materials have been widely studied by researchers. However, the development of efficient biobased flame retardants and convenient finishing methods was of great significance for the functional finishing of materials. Herein, a convenient and efficient flame retardant cotton fabric was prepared via layer by layer self-assembly (LbL) by alternating precipitation of a novel bio-based flame retardant phosphorylated sodium alginate (PSA) and alkylammonium functionalized siloxane (A-POSS). The effect of coating number on flame retardancy and thermal properties of coated cotton fabric was systematically studied. Thermogravimetric analysis (TGA) results showed that residual char contents of AP/PS-15BL under air and N2 atmospheres increased by 252.0% and 225.2%, respectively, compared with control cotton. In vertical flammability tests, both the AP/PS-10BL and AP/PS-15BL showed self-extinguishing behavior and successfully passed the UL-94 V-0 rating. More importantly, the LOI value of AP/PS-15BL was significantly increased to 35.0% from 20.0% of pure cotton fabric. Additionally, coated samples showed good mechanical properties and washable resistance. In CONE test, the peak heat release rate (PHRR) and total heat release rate (THR) of AP/PS-15BL decreased by 89.3% and 49.3% respectively, compared with control cotton. Therefore, this green and convenient flame-retardant finishing method has great application potential in the multi-functional finishing of cotton fabrics.


Subject(s)
Alginates , Cotton Fiber , Flame Retardants , Alginates/chemistry , Phosphorylation , Organosilicon Compounds/chemistry , Textiles , Thermogravimetry , Quaternary Ammonium Compounds/chemistry
8.
Talanta ; 276: 126273, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38776775

ABSTRACT

Ultrasensitive and rapid detection of low concentration of Escherichia coli O157: H7 (E. coli O157:H7) in food is essential for food safety and public health. In this study, A novel fluorescence signal amplification biosensor based on magnetic separation platform and red fluorescent carbon dots (R-CDs)-encapsulated breakable organosilica nanocapsules (BONs) for ultrasensitive detection of E. coli O157:H7 was established. Wulff-type boronic acid functionalized magnetic nanoparticles (MNPs@B-N/APBA) with broad-spectrum bacterial recognition ability were synthesized for the first time to recognize and capture E. coli O157: H7 in food samples. R-CDs@BONs labeled with anti-E. coli O157:H7 monoclonal antibody (mAb@R-CDs@BONs-NH2) were used as the second recognition element to ensure the specificity for E. coli O157:H7 and form MNPs@B-N/APBA∼ E. coli O157:H7∼mAb@R-CDs@BONs-NH2 sandwich complexes, followed by releasing R-CDs to generate amplified fluorescence response signals for quantitative detection of E. coli O157:H7. The proposed method had a limit of detection with 25 CFU/mL in pure culture and contaminated lettuce samples, which the whole detection process took about 120 min. This fluorescence signal amplification biosensor has the potential to detect other pathogens in food by altering specific antibodies.


Subject(s)
Biosensing Techniques , Carbon , Escherichia coli O157 , Quantum Dots , Escherichia coli O157/isolation & purification , Biosensing Techniques/methods , Carbon/chemistry , Quantum Dots/chemistry , Nanocapsules/chemistry , Fluorescent Dyes/chemistry , Fluorescence , Limit of Detection , Organosilicon Compounds/chemistry , Food Microbiology , Lactuca/microbiology , Lactuca/chemistry
9.
J Biol Inorg Chem ; 29(3): 303-314, 2024 04.
Article in English | MEDLINE | ID: mdl-38727821

ABSTRACT

This study demonstrates the potential of sono-photodynamic therapy as an effective approach for enhancing singlet oxygen generation using the synthesized Schiff-base diaxially substituted silicon phthalocyanines. In photochemical studies, the singlet oxygen quantum yields (Φ∆) were determined as 0.43 for Si1a, 0.94 for Q-Si1a, 0.58 for S-Si1a, and 0.49 for B-Sia1. In sono-photochemical studies, the Φ∆ values were reached to 0.67 for Si1a, 1.06 for Q-Si1a, 0.65 for S-Si1a, and 0.67 for B-Sia1. In addition, this study demonstrates the therapeutic efficacy of phthalocyanines synthesized as sensitizers on the PC3 prostate cancer cell line through in vitro experiments. The application of these treatment modalities exhibited notable outcomes, leading to a substantial decrease in cell viability within the PC3 prostate cancer cell line. These findings highlight the potential of utilizing these synthesized phthalocyanines as promising therapeutic agents for prostate cancer treatment.


Subject(s)
Cell Survival , Indoles , Organosilicon Compounds , Prostatic Neoplasms , Schiff Bases , Singlet Oxygen , Humans , Indoles/chemistry , Indoles/pharmacology , Schiff Bases/chemistry , Schiff Bases/pharmacology , Male , Singlet Oxygen/metabolism , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/metabolism , Organosilicon Compounds/chemistry , Organosilicon Compounds/pharmacology , Cell Survival/drug effects , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Photosensitizing Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Drug Screening Assays, Antitumor , PC-3 Cells , Photochemotherapy , Photochemical Processes , Cell Line, Tumor , Molecular Structure
10.
Analyst ; 149(13): 3522-3529, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38787653

ABSTRACT

Bioinspired nanochannel-based sensors have elicited significant interest because of their excellent sensing performance, and robust mechanical and tunable chemical properties. However, the existing designs face limitations due to material constraints, which hamper broader application possibilities. Herein, a heteromembrane system composed of a periodic mesoporous organosilica (PMO) layer with three-dimensional (3D) network nanochannels is constructed for glutathione (GSH) detection. The unique hierarchical pore architecture provides a large surface area, abundant reaction sites and plentiful interconnected pathways for rapid ionic transport, contributing to efficient and sensitive detection. Moreover, the thioether groups in nanochannels can be selectively cleaved by GSH to generate hydrophilic thiol groups. Benefiting from the increased hydrophilic surface, the proposed sensor achieves efficient GSH detection with a detection limit of 1.2 µM by monitoring the transmembrane ionic current and shows good recovery ranges in fetal bovine serum sample detection. This work paves an avenue for designing and fabricating nanofluidic sensing systems for practical and biosensing applications.


Subject(s)
Glutathione , Limit of Detection , Organosilicon Compounds , Glutathione/chemistry , Glutathione/analysis , Glutathione/blood , Porosity , Organosilicon Compounds/chemistry , Animals , Cattle , Biosensing Techniques/methods , Membranes, Artificial , Electrochemical Techniques/methods
11.
J Chromatogr A ; 1723: 464914, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38640880

ABSTRACT

This article describes the effect of modification with organic bases such as uracil (U) and polyethyleneimine (PEI) on the adsorption and chromatographic properties of poly(1-trimethylsilyl-1-propyne) (PTMSP) used as a stationary phase (SP) in packed and capillary columns. It was shown that the sorbents prepared on the basis of diatomite Chromosorb P NAW support and successively modified with 9 wt.% PTMSP and 1 wt.% U (or PEI) (PC-U and PC-PEI samples, respectively), have a mesoporous structure. The IR spectrum shows the presence of carbonyl groups in the sorbent modified with uracil. The impregnation of the Chromosorb P NAW + (9/1) wt.% PTMSP sorbent with a polyethyleneimine solution leads to the appearance in the spectrum of bands characterizing NH stretching and bending vibrations, as well as a band at 1310 cm-1 which can be attributed to CN bond vibrations. The chromatographic properties of the studied sorbents differ significantly from the properties of the initial PTMSP. Packed columns PC-U and PC-PEI, as well as capillary columns with a polyethyleneimine-modified PTMSP layer, allow one to selectively separate mixtures of polar and non-polar compounds and structural isomers of hydrocarbons. Methanol on these columns is eluted in the form of a symmetrical peak separately from propane, propylene and other associated hydrocarbon impurities in commercial (technical, target) n-butane.


Subject(s)
Polyethyleneimine , Polyethyleneimine/chemistry , Adsorption , Trimethylsilyl Compounds/chemistry , Uracil/chemistry , Uracil/analogs & derivatives , Organosilicon Compounds/chemistry , Porosity
12.
ACS Sens ; 9(5): 2383-2394, 2024 05 24.
Article in English | MEDLINE | ID: mdl-38687178

ABSTRACT

Oxygen plays a central role in aerobic metabolism, and while many approaches have been developed to measure oxygen concentration in biological environments over time, monitoring spatiotemporal changes in dissolved oxygen levels remains challenging. To address this, we developed a ratiometric core-shell organosilica nanosensor for continuous, real-time optical monitoring of oxygen levels in biological environments. The nanosensors demonstrate good steady state characteristics (KpSV = 0.40 L/mg, R2 = 0.95) and respond reversibly to changes in oxygen concentration in buffered solutions and report similar oxygen level changes in response to bacterial cell growth (Escherichia coli) in comparison to a commercial bulk optode-based sensing film. We further demonstrated that the oxygen nanosensors could be distributed within a growing culture of E. coli and used to record oxygen levels over time and in different locations within a static culture, opening the possibility of spatiotemporal monitoring in complex biological systems.


Subject(s)
Escherichia coli , Oxygen , Oxygen/metabolism , Oxygen/analysis , Escherichia coli/metabolism , Escherichia coli/isolation & purification , Biosensing Techniques/methods , Nanotechnology , Organosilicon Compounds/chemistry
13.
Biomacromolecules ; 25(5): 2728-2739, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38563621

ABSTRACT

Myopia is a global public health issue. Rigid contact lenses (RCLs) are an effective way to correct or control myopia. However, bioadhesion issues remain one of the significant obstacles limiting its clinical application. Although enhancing hydrophilicity through various surface treatments can mitigate this problem, the duration of effectiveness is short-lived and the processing involved is complex and costly. Herein, an antiadhesive RCLs material was designed via 8-armed methacrylate-POSS (8MA-POSS), and poly(ethylene glycol) methacrylate (PEGMA) copolymerization with 3-[tris(trimethylsiloxy)silyl] propyl methacrylate (TRIS). The POSS and PEG segments incorporated P(TRIS-co-PEGMA-co-8MA-POSS) (PTPM) material was obtained and their optical transparency, refractive index, resolution, hardness, surface charge, thermal features, and wettability were tested and optimized. The antibioadhesion activities, including protein, lipid, and bacteria, were evaluated as well. In vitro and in vivo results indicated that the optimized antibioadhesive PTPM materials present good biocompatibility and biosafety. Thus, such POSS and PEG segments containing material were a potential antibioadhesive RCL material option.


Subject(s)
Contact Lenses , Methacrylates , Organosilicon Compounds , Polyethylene Glycols , Polyethylene Glycols/chemistry , Methacrylates/chemistry , Animals , Organosilicon Compounds/chemistry , Organosilicon Compounds/pharmacology , Bacterial Adhesion/drug effects , Mice , Biocompatible Materials/chemistry , Humans , Myopia/drug therapy
14.
Colloids Surf B Biointerfaces ; 238: 113890, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38608462

ABSTRACT

A promising therapeutic strategy in cancer treatment merges photodynamic therapy (PDT) induced apoptosis with ferroptosis, a form of programmed cell death governed by iron-dependent lipid peroxidation. Given the pivotal role of mitochondria in ferroptosis, the development of photosensitizers that specifically provoke mitochondrial dysfunction and consequentially trigger ferroptosis via PDT is of significant interest. To this end, we have designed and synthesized a novel nanoparticle, termed FECTPN, tailored to address this requisite. FECTPN harnesses a trifecta of critical attributes: precision mitochondria targeting, photoactivation capability, pH-responsive drug release, and synergistic apoptosis-ferroptosis antitumor treatment. This nanoparticle was formulated by conjugating an asymmetric silicon phthalocyanine, Chol-SiPc-TPP, with the ferroptosis inducer Erastin onto a ferritin. The Chol-SiPc-TPP is a chemically crafted entity featuring cholesteryl (Chol) and triphenylphosphine (TPP) functionalities bonded axially to the silicon phthalocyanine, enhancing mitochondrial affinity and leading to effective PDT and subsequent apoptosis of cells. Upon cellular uptake, FECTPN preferentially localizes to mitochondria, facilitated by Chol-SiPc-TPP's targeting mechanics. Photoactivation induces the synchronized release of Chol-SiPc-TPP and Erastin in the mitochondria's alkaline domain, driving the escalation of both ROSs and lipid peroxidation. These processes culminate in elevated antitumor activity compared to the singular application of Chol-SiPc-TPP-mediated PDT. A notable observation is the pronounced enhancement in glutathione peroxidase-4 (GPX4) expression within MCF-7 cells treated with FECTPN and subjected to light exposure, reflecting intensified oxidative stress. This study offers compelling evidence that FECTPN can effectively induce ferroptosis and reinforces the paradigm of a synergistic apoptosis-ferroptosis pathway in cancer therapy, proposing a novel route for augmented antitumor treatments.


Subject(s)
Antineoplastic Agents , Apoptosis , Ferroptosis , Indoles , Mitochondria , Nanoparticles , Organosilicon Compounds , Photochemotherapy , Photosensitizing Agents , Indoles/chemistry , Indoles/pharmacology , Apoptosis/drug effects , Humans , Mitochondria/metabolism , Mitochondria/drug effects , Ferroptosis/drug effects , Nanoparticles/chemistry , Organosilicon Compounds/chemistry , Organosilicon Compounds/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemistry , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Particle Size , Cell Survival/drug effects , Surface Properties
15.
Int J Biol Macromol ; 267(Pt 1): 131575, 2024 May.
Article in English | MEDLINE | ID: mdl-38614178

ABSTRACT

Wound healing is a dynamic and complex process, it's urgent to develop new wound dressings with excellent performance to promote wound healing at the different stages. Here, a novel composite hydrogel dressing composed by silver nanoparticles (AgNPs) impregnated adenine-modified chitosan (CS-A) and octafunctionalized polyhedral oligomeric silsesquioxane (POSS) of benzaldehyde-terminated polyethylene glycol (POSS-PEG-CHO) solution was presented to solve the problem of wound infection. Modification of chitosan with adenine, not only can improve the water solubility of chitosan, but also introduce bioactive substances to promote cell proliferation. CS-A and POSS-PEG-CHO were cross-linked by Schiff-base reaction to form the injectable self-healing hydrogel. On this basis, AgNPs were added into the hydrogel, which endows the hydrogel with better antibacterial activity. Moreover, this kind of hydrogel exhibits excellent cell proliferation properties. Studies demonstrated that the hydrogel can significantly accelerate the closure of infected wounds. The histological analysis and immunofluorescence staining demonstrated that the wounds treated with the composite hydrogel exhibited fewer inflammatory cells, more collagen deposition and angiogenesis, faster regeneration of epithelial tissue. Above all, adenine-modified chitosan composite hydrogel with AgNPs loaded was considered as a dressing material with great application potential for promoting the healing of infected wounds.


Subject(s)
Adenine , Anti-Bacterial Agents , Cell Proliferation , Chitosan , Hydrogels , Metal Nanoparticles , Polyethylene Glycols , Silver , Wound Healing , Chitosan/chemistry , Chitosan/pharmacology , Wound Healing/drug effects , Cell Proliferation/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Polyethylene Glycols/chemistry , Silver/chemistry , Silver/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Animals , Metal Nanoparticles/chemistry , Adenine/pharmacology , Adenine/chemistry , Mice , Organosilicon Compounds/chemistry , Organosilicon Compounds/pharmacology , Rats , Humans , Wound Infection/drug therapy
16.
Angew Chem Int Ed Engl ; 63(25): e202404105, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38630059

ABSTRACT

Silyl ethers fulfil a fundamental role in synthetic organic chemistry as protecting groups and their selective cleavage is an important factor in their application. We present here for the first time two enzymes, SilE-R and SilE-S, which are able to hydrolyse silyl ethers. They belong to the stress-response dimeric A/B barrel domain (DABB) family and are able to cleave the Si-O bond with opposite enantiopreference. Silyl ethers containing aromatic, cyclic or aliphatic alcohols and, depending on the alcohol moiety, silyl functions as large as TBDMS are accepted. The X-ray crystal structure of SilE-R, determined to a resolution of 1.98 Å, in combination with mutational studies, revealed an active site featuring two histidine residues, H8 and H79, which likely act synergistically as nucleophile and Brønsted base in the hydrolytic mechanism, which has not previously been described for enzymes. Although the natural function of SilE-R and SilE-S is unknown, we propose that these 'silyl etherases' may have significant potential for synthetic applications.


Subject(s)
Ethers , Hydrolysis , Ethers/chemistry , Stereoisomerism , Models, Molecular , Crystallography, X-Ray , Organosilicon Compounds/chemistry , Organosilicon Compounds/chemical synthesis , Molecular Structure , Catalytic Domain
17.
Chemosphere ; 354: 141681, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38467199

ABSTRACT

Dimethylsilanediol (DMSD) is the common breakdown product of methylsiloxanes such as polydimethylsiloxane (PDMS) and volatile methylsiloxanes (VMS) in soil. In this work, we first present a sorbent selection experiment aiming to identify a sorbent that can trap gas-phase DMSD without causing DMSD condensation and VMS hydrolysis at environmentally relevant humidities. With a proper sorbent (Tenax) identified, the volatilization of DMSD from water and various wet soil and soil materials were measured in a controlled environment. It was demonstrated that DMSD underwent volatilization after soil water was completely evaporated. Various types of soil constituents show drastic differences in preventing DMSD from volatilization. Analysis of the sorbent-captured products provides further insight, most notably that virtually no cyclic methylsiloxanes are formed during the volatilization of DMSD from water or soil materials, except in one extreme case where only traces are detected.


Subject(s)
Organosilicon Compounds , Soil , Water , Volatilization
18.
Int J Pharm ; 654: 123962, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38432450

ABSTRACT

The development of pediatric oral drugs is hampered by a lack of predictive simulation tools. These tools, in turn, require data on the physiological variables that influence oral drug absorption, including the expression of drug transporter proteins (DTPs) and drug-metabolizing enzymes (DMEs) in the intestinal tract. The expression of hepatic DTPs and DMEs shows age-related changes, but there are few data on protein levels in the intestine of children. In this study, tissue was collected from different regions of the small and large intestine from neonates (i.e., surgically removed tissue) and from pediatric patients (i.e., gastroscopic duodenal biopsies). The protein expression of clinically relevant DTPs and DMEs was determined using a targeted mass spectrometry approach. The regional distribution of DTPs and DMEs was similar to adults. Most DTPs, with the exception of MRP3, MCT1, and OCT3, and all DMEs showed the highest protein expression in the proximal small intestine. Several proteins (i.e., P-gp, ASBT, CYP3A4, CYP3A5, CYP2C9, CYP2C19, and UGT1A1) showed an increase with age. Such increase appeared to be even more pronounced for DMEs. This exploratory study highlights the developmental changes in DTPs and DMEs in the intestinal tract of the pediatric population. Additional evaluation of protein function in this population would elucidate the implications of the presented changes in protein expression on absorption of orally administered drugs in neonates and pediatric patients.


Subject(s)
Carrier Proteins , Imidazoles , Membrane Transport Proteins , Organosilicon Compounds , Adult , Infant, Newborn , Humans , Child , Membrane Transport Proteins/metabolism , Intestine, Small/metabolism , Liver/metabolism
19.
Mikrochim Acta ; 191(3): 153, 2024 02 23.
Article in English | MEDLINE | ID: mdl-38393379

ABSTRACT

This study introduces aptamer-functionalized polyhedral oligomeric silsesquioxane (POSS) nanoparticles for adenosine triphosphate (ATP) detection where the POSS nanoparticles were synthesized in a one-step, continuous flow microfluidic reactor utilizing thermal polymerization. A microemulsion containing POSS monomers was generated in the microfluidic reactor which was designed to prevent clogging by using a continuous oil flow around the emulsion during thermal polymerization. Surfaces of POSS nanoparticles were biomimetically modified by polydopamine. The aptamer sequence for ATP was successfully attached to POSS nanoparticles. The aptamer-modified POSS nanoparticles were tested for affinity-based biosensor applications using ATP as a model molecule. The nanoparticles were able to capture ATP molecules successfully with an affinity constant of 46.5 [Formula: see text]M. Based on this result, it was shown, for the first time, that microfluidic synthesis of POSS nanoparticles can be utilized in designing aptamer-functionalized nanosystems for biosensor applications. The integration of POSS in biosensing technologies not only exemplifies the versatility and efficacy of these nanoparticles but also marks a significant contribution to the field of biorecognition and sample preparation.


Subject(s)
Biosensing Techniques , Nanoparticles , Organosilicon Compounds , Adenosine Triphosphate , Microfluidics , Oligonucleotides
20.
Chemosphere ; 352: 141454, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38354863

ABSTRACT

Dimethylsilanediol (DMSD) is the degradation product of methylsiloxane polymers and oligomers such as volatile cyclic methylsiloxanes (cVMS). To better understand the environmental fate of this key degradation product, we conducted a three-part study on the movement of DMSD in soil. The objective of this third and final study was to determine the fate of DMSD in soil-plant systems under constant irrigation. Soil columns were constructed using two soils with the upper 20 cm layers spiked with 14C-labeled DMSD. Corn seedlings were transplanted into the soil columns and placed in a field plot underneath a transparent cover that prevented rainwater from reaching the soil columns while allowing soil water to be volatilized freely. The soil-plant columns were regularly irrigated with known amounts of DMSD-free plant growth solution to sustain the plant growth. At pre-determined time intervals (15-67 days), the plant and soil columns were sectioned and the distribution of 14Corganosilicon species in the soil profile and plant parts was determined using a combination of Liquid Scintillation Counting and High-Performance Liquid Chromatography-Flow Scintillation Analysis, while soil water loss was determined gravimetrically. It was found that the majority (>92 %) of DMSD initially spiked into the soil was removed from the soil-plant systems. Although DMSD was transported from the soil to the plant, it was subsequently volatilized from the plant via transpiration, with only a small fraction (∼5%) remaining at the conclusion of the experiments. In addition, little non-extractable DMSD was found in the top layer of soil in the soil-plant systems, suggesting that the air-drying of soil is a necessary pre-condition for the formation of such non-extractable silanol residue on topsoil.


Subject(s)
Organosilicon Compounds , Soil Pollutants , Water Pollutants, Chemical , Soil , Water , Water Pollutants, Chemical/analysis , Soil Pollutants/analysis
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