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1.
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
2.
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
3.
J Biol Inorg Chem ; 29(3): 303-314, 2024 Apr.
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
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 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
6.
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
7.
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
8.
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
9.
ACS Sens ; 9(5): 2383-2394, 2024 May 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
10.
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
11.
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
12.
ACS Sens ; 9(3): 1482-1488, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38416572

ABSTRACT

A pH colorimetric sensor array (CSA) was prepared on a nitrocellulose membrane and used for accurate pH measurement in highly concentrated saline solutions. The CSAs consisted of sensing spots made of a suitable OrMoSil polymer prepared from organo-fluorinated-silane precursors and/or organosilane with tetraethyl orthosilicate hosting an acid-base indicator. Four CSAs were prepared: D, 1F, 2F, and 3F. In D, a nonfluorinated organosilane was present. From 1F to 3F, the concentration of the fluorinated organosilane increased and improved the pH measurement accuracy in highly saline concentrations. No recalibrations were required, and the analytical signal was stable in time. D, 1F, 2F, and 3F were deposited in triplicate, and they were prepared to work in the seawater pH interval (7.50-8.50). The use of fluorinated precursors led to a lower pH prediction error and tailored the interval of the CSA at more basic pH values so that the inflection points of the sigmoidal calibrations of D, 1F, 2F, and 3F moved from 6.97 to 7.98. The overall pH prediction error was 0.10 pH (1F), 0.02 pH (2F), and 0.04 pH units (3F). The CSAs were stable, reversible, reusable, and independent of salinity (S) between 20 and 40. The performances of the CSA were compared with those of a glass electrode, whose pHNIST values were converted in the pHSWS scale through a conversion equation. Being unaffected by the typical drawback of the glass electrode, the CSAs can be used directly in seawater real samples, and it validated the proposed conversion equation.


Subject(s)
Colorimetry , Organosilicon Compounds , Hydrogen-Ion Concentration , Seawater , Electrodes , Saline Solution
13.
Drug Saf ; 47(5): 475-485, 2024 May.
Article in English | MEDLINE | ID: mdl-38401041

ABSTRACT

INTRODUCTION AND OBJECTIVE: The European Medicines Agency (EMA) maintains a list of designated medical events (DMEs), events that are inherently serious and are prioritized for signal detection, irrespective of statistical criteria. We have analysed the results of our previously published scoping review to determine whether DME signals differ from those of other adverse events in terms of time to communication and characteristics of supporting reports of suspected adverse drug reactions. METHODS: For all signals, we obtained the launch year of medicinal products from textbooks or regulatory agencies, extracted the year of the first report in VigiBase and calculated the interval between the first report and communication (time to communication, TTC). We further retrieved the average completeness (via vigiGrade) of the reports in each case series in the years before the communication. We categorised as DME signals those concerning an event in the EMA's list. We described the two groups of signals using medians and interquartile ranges (IQR) and compared them using the Brunner-Munzel test, calculating 95% confidence intervals (95% CI) and P values. RESULTS: Of 4520 signals, 919 concerned DMEs and 3601 concerned non-DMEs. Signals of DMEs were supported by a median of 15 reports (IQR 6-38 reports) with a completeness score of 0.52 (IQR 0.43-0.62) and signals of non-DMEs by 20 reports (IQR 6-84 reports) with a completeness score of 0.46 (IQR 0.38-0.56). The probability that a random DME signal was supported by fewer reports than non-DME signals was 0.56 (95% CI 0.54-0.58, P < 0.001) and that of one having lower average completeness was 0.39 (95% CI 0.36-0.41, P < 0.001). The median TTCs of DME and non-DME signals did not differ (10 years), but the TTC was as low as 2 years when signals (irrespective of classification) were supported by reports whose average completeness was > 0.80. CONCLUSIONS: Signals of designated medical events were supported by fewer reports and higher completeness scores than signals of other adverse events. Although statistically significant, the differences in effect sizes between the two groups were small. This suggests that listing certain adverse events as DMEs is not having the expected effect of encouraging a focus on reports of the types of suspected adverse reactions that deserve special attention. Further enhancing the completeness of the reports of suspected adverse drug reactions supporting signals of designated medical events might shorten their time to communication and reduce the number of reports required to support them.


Subject(s)
Adverse Drug Reaction Reporting Systems , Drug-Related Side Effects and Adverse Reactions , Imidazoles , Organosilicon Compounds , Humans , Drug-Related Side Effects and Adverse Reactions/epidemiology , Probability , Communication
14.
Chemosphere ; 352: 141478, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38364924

ABSTRACT

Dimethylsilanediol (DMSD) is a primary degradation product of silicone materials in the environment. Due to its low air/water partition coefficient and low soil/water distribution coefficient, this compound is not expected to undergo sorption and volatilization in wet soil. In an accompanying paper, we confirm that under controlled indoor conditions in test tubes, there is little to no volatilization of DMSD from soil and soil constituents if soil is wet. However, a significant amount of DMSD was volatilized when the soil substrates became air dried. Given the importance of water on the partition and fate of DMSD, we now report a continuation of this study focusing on the relation between DMSD removal and water loss in re-constituted soil columns under outdoor conditions. Consistent with predictions based on its partition properties and reconciling this evidence with previously reported field and laboratory studies, DMSD distribution was found to be largely dependent on water partitioning. The results suggested that DMSD moved upward in soil profile as soil water was evaporated from topmost layers with little DMSD retention by the soil matrix. As soil dried, a fraction of DMSD was sorbed by the soil matrix in the topmost layer, while most of the spiked radio-labeled DMSD was removed from soil through volatilization.


Subject(s)
Organosilicon Compounds , Soil Pollutants , Water/chemistry , Soil , Silicones , Soil Pollutants/analysis
15.
PeerJ ; 12: e16856, 2024.
Article in English | MEDLINE | ID: mdl-38313008

ABSTRACT

Background: Skin flap transplantation is one of the effective methods to treat the diabetes-related foot ulceration, but the intrinsic damage to vessels in diabetes mellitus (DM) leads to the necrosis of skin flaps. Therefore, the discovery of a non-invasive and effective approach for promoting the survival of flaps is of the utmost importance. Electrical stimulation (ES) promotes angiogenesis and increases the proliferation, migration, and elongation of endothelial cells, thus being a potential effective method to improve flap survival. Objective: The purpose of this study was to elucidate the mechanism used by ES to effectively restore the impaired function of endothelial cells caused by diabetes. Methods: A total of 79 adult male Sprague-Dawley rats were used in this study. Gene and protein expression was assessed by PCR and western blotting, respectively. Immunohistochemistry and hematoxylin-eosin staining were performed to evaluate the morphology and density of the microvessels in the flap. Results: The optimal duration for preconditioning the flap with ES was 7 days. The flap survival area percentage and microvessels density in the DMES group were markedly increased compared to the DM group. VEGF, MMP2, and MMP9 protein expression was significantly upregulated. ROS intensity was significantly decreased and GSH concentration was increased. The expression of IL-1ß, MCP­1, cleaved caspase-3, and Bax were downregulated in the DMES group, while TGF-ß expression was upregulated. Conclusions: ES improves the angiogenesis in diabetic ischemic skin flaps by attenuating oxidative stress-mediated inflammation and apoptosis, eventually increasing their viability.


Subject(s)
Diabetes Mellitus , Imidazoles , Organosilicon Compounds , Perforator Flap , Rats , Male , Animals , Rats, Sprague-Dawley , Angiogenesis , Endothelial Cells , Neovascularization, Physiologic , Apoptosis , Inflammation , Oxidative Stress , Electric Stimulation
16.
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
17.
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
18.
Int J Pharm ; 652: 123852, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38280501

ABSTRACT

This study comprises the comprehensive toxicological assessment of thiolated organosilica nanoparticles (NPs) synthesised from 3-mercaptopropyltrimethoxysilane (MPTS). We investigated the influence of three different types of nanoparticles synthesised from 3-mercaptopropyltrimethoxysilane: the starting thiolated silica (Si-NP-SH) and their derivatives prepared by surface PEGylation with PEG 750 (Si-NP-PEG750) and 5000 Da (Si-NP-PEG5000) on biological subjects from in vitro to in vivo experiments to explore the possible applications of those nanoparticles in biomedical research. As a result of this study, we generated a comprehensive understanding of the toxicological properties of these nanoparticles, including their cytotoxicity in different cell lines, hemolytic properties, in vitro localisation, mucosal irritation properties and biodistribution in BALB/c mice. Our findings indicate that all three types of nanoparticles can be considered safe and have promising prospects for use in biomedical applications. Nanoparticles did not affect the viability of HPF, MCF7, HEK293 and A549 cell lines at low concentrations (up to 100 µg/mL); moreover, they did not cause organ damage to BALB/c mice at concentrations of 10 mg/kg. The outcomes of this study enhance our understanding of the impact of organosilica nanoparticles on health and the environment, which is vital for developing silica nanoparticle-based drug delivery systems and provides opportunities to expand the applications of organosilica nanoparticles.


Subject(s)
Nanoparticles , Organosilicon Compounds , Humans , Mice , Animals , Tissue Distribution , HEK293 Cells , Nanoparticles/toxicity , Silicon Dioxide/toxicity , Polyethylene Glycols/toxicity
19.
J Hazard Mater ; 466: 133470, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38246053

ABSTRACT

Quaternary ammonium compounds (QACs) are commonly used as disinfectants for industrial, medical, and residential applications. However, adverse health outcomes have been reported. Therefore, biocompatible disinfectants must be developed to reduce these adverse effects. In this context, QACs with various alkyl chain lengths (C12-C18) were synthesized by reacting QACs with the counterion silane. The antimicrobial activities of the novel compounds against four strains of microorganisms were assessed. Several in vivo assays were conducted on Drosophila melanogaster to determine the toxicological outcomes of Si-QACs, followed by computational analyses (molecular docking, simulation, and prediction of skin sensitization). The in vivo results were combined using a cheminformatics approach to understand the descriptors responsible for the safety of Si-QAC. Si-QAC-2 was active against all tested bacteria, with minimal inhibitory concentrations ranging from 13.65 to 436.74 ppm. Drosophila exposed to Si-QAC-2 have moderate-to-low toxicological outcomes. The molecular weight, hydrophobicity/lipophilicity, and electron diffraction properties were identified as crucial descriptors for ensuring the safety of the Si-QACs. Furthermore, Si-QAC-2 exhibited good stability and notable antiviral potential with no signs of skin sensitization. Overall, Si-QAC-2 (C14) has the potential to be a novel disinfectant.


Subject(s)
Disinfectants , Organosilicon Compounds , Quaternary Ammonium Compounds , Animals , Quaternary Ammonium Compounds/toxicity , Silanes , Disinfectants/toxicity , Drosophila melanogaster , Molecular Docking Simulation
20.
Photochem Photobiol ; 100(1): 52-66, 2024.
Article in English | MEDLINE | ID: mdl-37431229

ABSTRACT

To treat a life-threatening disease like cancer, photodynamic therapy (PDT) and sonodynamic therapy (SDT) methods were combined into sono-photodynamic therapy (SPDT) as an effective therapeutic solution. Each day, the usage of phthalocyanine sensitizers increases in the therapeutic applications as they have the ability to produce more reactive oxygen species. In this context, a new diaxially silicon phthalocyanine sensitizer, containing triazole and tert-butyl groups, was synthesized. After elucidating the structure of the complex with elemental analysis, FT-IR, UV-Vis, MALDI-TOF MS and 1 H NMR, its photophysical, photochemical and sono-photochemical properties were examined. When singlet oxygen generation capacity of the new synthesized silicon phthalocyanine complex was determined and compared among photochemical (PDT; Ð¤Δ = 0.59 in DMSO, 0.44 in THF, 0.47 in toluene) and sonophotochemical (SPDT; Ð¤Δ = 0.88 in dimethyl sulfoxide (DMSO), 0.60 in tetrahydrofuran (THF), 0.65 in toluene) methods, it can be said that the complex is a successful sono-photosensitizer that can be used as a good SPDT agent in vitro or in vivo future studies.


Subject(s)
Indoles , Organosilicon Compounds , Photochemotherapy , Singlet Oxygen , Singlet Oxygen/chemistry , Dimethyl Sulfoxide , Spectroscopy, Fourier Transform Infrared , Photosensitizing Agents/therapeutic use , Photosensitizing Agents/chemistry , Toluene
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