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1.
Sci Rep ; 14(1): 10566, 2024 05 08.
Article En | MEDLINE | ID: mdl-38719873

Conventional wastewater treatment processes are often unable to remove antibiotics with resistant compounds and low biological degradation. The need for advanced and sustainable technologies to remove antibiotics from water sources seems essential. In this regard, the effectiveness of a spinning disc photocatalytic reactor (SDPR) equipped with a visible light-activated Fe3O4@SiO2-NH2@CuO/ZnO core-shell (FSNCZ CS) thin film photocatalyst was investigated for the decomposition of amoxicillin (AMX), a representative antibiotic. Various characterization techniques, such as TEM, FESEM, EDX, AFM, XRD, and UV-Vis-DRS, were employed to study the surface morphology, optoelectronic properties, and nanostructure of the FSNCZ CS. Key operating parameters such as irradiation time, pH, initial AMX concentration, rotational speed, and solution flow rate were fine-tuned for optimization. The results indicated that the highest AMX decomposition (98.7%) was attained under optimal conditions of 60 min of irradiation time, a rotational speed of 350 rpm, a solution flow rate of 0.9 L/min, pH of 5, and an initial AMX concentration of 20 mg/L. Moreover, during the 60 min irradiation time, more than 69.95% of chemical oxygen demand and 61.2% of total organic carbon were removed. After the photocatalytic decomposition of AMX, there is a substantial increase in the average oxidation state and carbon oxidation state in SDPR from 1.33 to 1.94 and 3.2, respectively. Active species tests confirmed that ·OH and ·O2- played a dominant role in AMX decomposition. The developed SDPR, which incorporates a reusable and robust FSNCZ CS photocatalyst, demonstrates promising potential for the decomposition of organic compounds.


Amoxicillin , Anti-Bacterial Agents , Light , Nanostructures , Catalysis , Anti-Bacterial Agents/chemistry , Nanostructures/chemistry , Amoxicillin/chemistry , Water Pollutants, Chemical/chemistry , Copper/chemistry , Zinc Oxide/chemistry , Silicon Dioxide/chemistry , Water Purification/methods
2.
J Nanobiotechnology ; 22(1): 249, 2024 May 14.
Article En | MEDLINE | ID: mdl-38745193

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.


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
3.
Sci Rep ; 14(1): 10418, 2024 05 06.
Article En | MEDLINE | ID: mdl-38710793

A new drug delivery system using an asymmetric polyethersulfone (PES) membrane modified by SBA-15 and glutamine-modified SBA-15 (SBA-Q) was prepared in this study by the aim of azithromycin delivery enhancement in both in vitro and ex vivo experiments. The research focused on optimizing membrane performance by adjusting critical parameters including drug concentration, membrane thickness, modifier percentage, polymer percentage, and pore maker percentage. To characterize the fabricated membranes, various techniques were employed, including scanning electron microscopy, water contact angle, and tensile strength assessments. Following optimization, membrane composition of 17% PES, 2% polyvinylpyrrolidone, 1% SBA-15, and 0.5% SBA-Q emerged as the most effective. The optimized membranes demonstrated a substantial increase in drug release (906 mg/L) compared to the unmodified membrane (440 mg/L). The unique membrane structure, with a dense top layer facilitating sustained drug release and a porous sub-layer acting as a drug reservoir, contributed to this improvement. Biocompatibility assessments, antibacterial activity analysis, blood compatibility tests, and post-diffusion tissue integrity evaluations confirmed the promising biocompatibility of the optimized membranes. Moreover, long-term performance evaluations involving ten repeated usages underscored the reusability of the optimized membrane, highlighting its potential for sustained and reliable drug delivery applications.


Anti-Bacterial Agents , Drug Delivery Systems , Membranes, Artificial , Polymers , Silicon Dioxide , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Silicon Dioxide/chemistry , Polymers/chemistry , Porosity , Sulfones/chemistry , Sulfones/administration & dosage , Drug Liberation , Animals , Azithromycin/administration & dosage , Azithromycin/pharmacokinetics , Azithromycin/chemistry , Azithromycin/pharmacology , Humans
4.
Pak J Pharm Sci ; 37(1(Special)): 235-243, 2024 Jan.
Article En | MEDLINE | ID: mdl-38747275

Stimulus-responsive mesoporous silica nanoparticles (MSNs) have displayed great potentiality for controlled-release and targeted drug delivery. In the current work, a supercritical fluid method was utilized to successfully prepare cinnamon oil loaded into chitosan grafted MSNs (CO@CS-MSNs). The influencing factors of drug loads, such as pressure, temperature, impregnation time and depressure time, were investigated. The structure of CO@CS-MSNs was demonstrated with Fourier-transform infrared (FT-IR) spectroscopy, transmission electron microscope (TEM), scanning electron microscopy (SEM), thermogravimetry (TG) as well as X-ray diffraction (XRD). The drug release assays in vitro at various pH conditions displayed that CO@CS-MSNs had an excellent pH-responsive release behavior, which confirmed that CO was loaded successfully into the CO@CS-MSNs. The findings indicated that the supercritical fluid approach is a non-destructive and efficient approach for stimulus-responsive MSNs, which is expected to further expand its application range.


Carbon Dioxide , Chitosan , Cinnamomum zeylanicum , Drug Liberation , Nanoparticles , Silicon Dioxide , Chitosan/chemistry , Silicon Dioxide/chemistry , Nanoparticles/chemistry , Hydrogen-Ion Concentration , Carbon Dioxide/chemistry , Porosity , Cinnamomum zeylanicum/chemistry , Drug Carriers/chemistry , Oils, Volatile/chemistry , Oils, Volatile/administration & dosage , X-Ray Diffraction , Spectroscopy, Fourier Transform Infrared , Microscopy, Electron, Scanning , Delayed-Action Preparations
5.
J Agric Food Chem ; 72(19): 10781-10793, 2024 May 15.
Article En | MEDLINE | ID: mdl-38709780

In this study, 20-day-old soybean plants were watered with 100 mL of 100 mM NaCl solution and sprayed with silica nanoparticles (SiO2 NPs) or potassium silicate every 3 days over 15 days, with a final dosage of 12 mg of SiO2 per plant. We assessed the alterations in the plant's growth and physiological traits, and the responses of bacterial microbiome within the leaf endosphere, rhizosphere, and root endosphere. The result showed that the type of silicon did not significantly impact most of the plant parameters. However, the bacterial communities within the leaf and root endospheres had a stronger response to SiO2 NPs treatment, showing enrichment of 24 and 13 microbial taxa, respectively, compared with the silicate treatment, which led to the enrichment of 9 and 8 taxonomic taxa, respectively. The rhizosphere bacterial communities were less sensitive to SiO2 NPs, enriching only 2 microbial clades, compared to the 8 clades enriched by silicate treatment. Furthermore, SiO2 NPs treatment enriched beneficial genera, such as Pseudomonas, Bacillus, and Variovorax in the leaf and root endosphere, likely enhancing plant growth and salinity stress resistance. These findings highlight the potential of SiO2 NPs for foliar application in sustainable farming by enhancing plant-microbe interactions to improve salinity tolerance.


Bacteria , Glycine max , Nanoparticles , Rhizosphere , Silicon , Glycine max/microbiology , Glycine max/growth & development , Glycine max/drug effects , Glycine max/chemistry , Nanoparticles/chemistry , Bacteria/classification , Bacteria/genetics , Bacteria/drug effects , Bacteria/isolation & purification , Bacteria/growth & development , Silicon/pharmacology , Silicon/chemistry , Plant Roots/microbiology , Plant Roots/growth & development , Plant Roots/drug effects , Soil Microbiology , Microbiota/drug effects , Plant Leaves/chemistry , Plant Leaves/microbiology , Plant Leaves/growth & development , Endophytes/physiology , Endophytes/drug effects , Silicon Dioxide/chemistry , Salt Stress
6.
BMC Oral Health ; 24(1): 557, 2024 May 13.
Article En | MEDLINE | ID: mdl-38735940

BACKGROUND: Dental resin-based composites are widely recognized for their aesthetic appeal and adhesive properties, which make them integral to modern restorative dentistry. Despite their advantages, adhesion and biomechanical performance challenges persist, necessitating innovative strategies for improvement. This study addressed the challenges associated with adhesion and biomechanical properties in dental resin-based composites by employing molecular docking and dynamics simulation. METHODS: Molecular docking assesses the binding energies and provides valuable insights into the interactions between monomers, fillers, and coupling agents. This investigation prioritizes SiO2 and TRIS, considering their consistent influence. Molecular dynamics simulations, executed with the Forcite module and COMPASS II force field, extend the analysis to the mechanical properties of dental composite complexes. The simulations encompassed energy minimization, controlled NVT and NPT ensemble simulations, and equilibration stages. Notably, the molecular dynamics simulations spanned a duration of 50 ns. RESULTS: SiO2 and TRIS consistently emerged as influential components, showcasing their versatility in promoting solid interactions. A correlation matrix underscores the significant roles of van der Waals and desolvation energies in determining the overall binding energy. Molecular dynamics simulations provide in-depth insights into the mechanical properties of dental composite complexes. HEMA-SiO2-TRIS excelled in stiffness, BisGMA-SiO2-TRIS prevailed in terms of flexural strength, and EBPADMA-SiO2-TRIS offered a balanced combination of mechanical properties. CONCLUSION: These findings provide valuable insights into optimizing dental composites tailored to diverse clinical requirements. While EBPADMA-SiO2-TRIS demonstrates distinct strengths, this study emphasizes the need for further research. Future investigations should validate the computational findings experimentally and assess the material's response to dynamic environmental factors.


Biocompatible Materials , Composite Resins , Molecular Docking Simulation , Molecular Dynamics Simulation , Silicon Dioxide , Composite Resins/chemistry , Silicon Dioxide/chemistry , Biocompatible Materials/chemistry , Dental Materials/chemistry , Methacrylates/chemistry , Polyurethanes/chemistry , Polymethacrylic Acids/chemistry , Polyethylene Glycols/chemistry , Acrylic Resins/chemistry
7.
Mikrochim Acta ; 191(6): 303, 2024 05 06.
Article En | MEDLINE | ID: mdl-38709340

A platform was designed based on Fe3O4 and CsPbBr3@SiO2 for integrated magnetic enrichment-fluorescence detection of Salmonella typhimurium, which significantly simplifies the detection process and enhances the working efficiency. Fe3O4 served as a magnetic enrichment unit for the capture of S. typhimurium. CsPbBr3@SiO2 was employed as a fluorescence-sensing unit for quantitative signal output, where SiO2 was introduced to strengthen the stability of CsPbBr3, improve its biomodificability, and prevent lead leakage. More importantly, the SiO2 shell shows neglectable absorption or scattering towards fluorescence, making the CsPbBr3@SiO2 exhibit a high quantum yield of 74.4%. After magnetic enrichment, the decreasing rate of the fluorescence emission intensity of the CsPbBr3@SiO2 supernatant at 527 nm under excitation light at UV 365 nm showed a strong linear correlation with S. typhimurium concentration of 1 × 102~1 × 108 CFU∙mL-1, and the limit of detection (LOD) reached 12.72 CFU∙mL-1. This platform has demonstrated outstanding stability, reproducibility, and resistance to interference, which provides an alternative for convenient and quantitative detection of S. typhimurium.


Fluorescent Dyes , Limit of Detection , Salmonella typhimurium , Silicon Dioxide , Salmonella typhimurium/isolation & purification , Silicon Dioxide/chemistry , Fluorescent Dyes/chemistry , Spectrometry, Fluorescence/methods , Lead/chemistry , Point-of-Care Systems , Sulfides/chemistry , Magnetite Nanoparticles/chemistry , Humans
8.
Mol Biol Rep ; 51(1): 623, 2024 May 06.
Article En | MEDLINE | ID: mdl-38710891

BACKGROUND: An increase in cancer stem cell (CSC) populations and their resistance to common treatments could be a result of c-Myc dysregulations in certain cancer cells. In the current study, we investigated anticancer effects of c-Myc decoy ODNs loaded-poly (methacrylic acid-co-diallyl dimethyl ammonium chloride) (PMA-DDA)-coated silica nanoparticles as carriers on cancer-like stem cells (NTERA-2). METHODS AND RESULTS: The physicochemical characteristics of the synthesized nanocomposites (SiO2@PMA-DDA-DEC) were analyzed using FT-IR, DLS, and SEM techniques. UV-Vis spectrophotometer was applied to analyze the release pattern of decoy ODNs from the nanocomposite. Furthermore, uptake, cell viability, apoptosis, and cell cycle assays were used to investigate the anticancer effects of nanocomposites loaded with c-Myc decoy ODNs on NTERA-2 cancer cells. The results of physicochemical analytics demonstrated that SiO2@PMA-DDA-DEC nanocomposites were successfully synthesized. The prepared nanocomposites were taken up by NTERA-2 cells with high efficiency, and could effectively inhibit cell growth and increase apoptosis rate in the treated cells compared to the control group. Moreover, SiO2@PMA-DDA nanocomposites loaded with c-Myc decoy ODNs induced cell cycle arrest at the G0/G1 phase in the treated cells. CONCLUSIONS: The conclusion drawn from this study is that c-Myc decoy ODN-loaded SiO2@PMA-DDA nanocomposites can effectively inhibit cell growth and induce apoptosis in NTERA-2 cancer cells. Moreover, given that a metal core is incorporated into this synthetic nanocomposite, it could potentially be used in conjunction with irradiation as part of a decoy-radiotherapy combinational therapy in future investigations.


Apoptosis , Cell Proliferation , Nanoparticles , Neoplastic Stem Cells , Proto-Oncogene Proteins c-myc , Humans , Apoptosis/drug effects , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Proto-Oncogene Proteins c-myc/genetics , Cell Proliferation/drug effects , Nanoparticles/chemistry , Cell Line, Tumor , Nanocomposites/chemistry , Polyelectrolytes/chemistry , Oligodeoxyribonucleotides/pharmacology , Oligodeoxyribonucleotides/chemistry , Cell Survival/drug effects , Silicon Dioxide/chemistry , Polyamines/chemistry , Polyamines/pharmacology , Cell Cycle/drug effects
9.
J Sep Sci ; 47(9-10): e2300949, 2024 May.
Article En | MEDLINE | ID: mdl-38726739

Hydrophilic interaction liquid chromatography (HILIC) has been widely applied to challenging analysis in biomedical and pharmaceutical fields, bridging the gap between normal-phase high-performance liquid chromatography and reversed-phase high-performance liquid chromatography (RP-HPLC). This paper comprehensively explores the retention mechanisms of amitriptyline and its impurities A, B, C, D, F, and G on amide, amino, diol, and silica columns. Dual HILIC/RP-HPLC retention mechanisms were developed, and transitional points between HILIC and RP-HPLC mechanisms were calculated on amide, diol, and silica columns. Adsorption and partition contributions to overall retention mechanisms were evaluated using Python software in HILIC and RP-HPLC regions. The cation exchange mechanism dominates overall retention for ionized analytes in the silica column (R2 > 0.995), whereas the retention of ionized analytes increases with pH. Impacts of acetonitrile content, buffer ionic strength, and pH, along with their interactions on the retention of ionized analytes in the silica column, were determined using the chemometric approach. Acetonitrile content showed the most significant impact on the retention mechanisms. These findings highlight that a detailed investigation into retention mechanisms provides notable insights into factors influencing analyte retention and separation, promising valuable guidance for future analysis.


Amides , Amitriptyline , Hydrophobic and Hydrophilic Interactions , Silicon Dioxide , Silicon Dioxide/chemistry , Amitriptyline/analysis , Amitriptyline/chemistry , Amides/chemistry , Amides/analysis , Chromatography, High Pressure Liquid , Drug Contamination , Chromatography, Liquid/methods , Molecular Structure
10.
Biomed Mater ; 19(4)2024 May 10.
Article En | MEDLINE | ID: mdl-38697132

During the process of malignant tumor treatment, photodynamic therapy (PDT) exerts poor efficacy due to the hypoxic environment of the tumor cells, and long-time chemotherapy reduces the sensitivity of tumor cells to chemotherapy drugs due to the presence of drug-resistant proteins on the cell membranes for drug outward transportation. Therefore, we reported a nano platform based on mesoporous silica coated with polydopamine (MSN@PDA) loading PDT enhancer MnO2, photosensitizer indocyanine green (ICG) and chemotherapeutic drug doxorubicin (DOX) (designated as DMPIM) to achieve a sequential release of different drugs to enhance treatment of malignant tumors. MSN was first synthesized by a template method, then DOX was loaded into the mesoporous channels of MSN, and locked by the PDA coating. Next, ICG was modified by π-π stacking on PDA, and finally, MnO2layer was accumulated on the surface of DOX@MSN@PDA- ICG@MnO2, achieving orthogonal loading and sequential release of different drugs. DMPIM first generated oxygen (O2) through the reaction between MnO2and H2O2after entering tumor cells, alleviating the hypoxic environment of tumors and enhancing the PDT effect of sequentially released ICG. Afterwards, ICG reacted with O2in tumor tissue to produce reactive oxygen species, promoting lysosomal escape of drugs and inactivation of p-glycoprotein (p-gp) on tumor cell membranes. DOX loaded in the MSN channels exhibited a delay of approximately 8 h after ICG release to exert the enhanced chemotherapy effect. The drug delivery system achieved effective sequential release and multimodal combination therapy, which achieved ideal therapeutic effects on malignant tumors. This work offers a route to a sequential drug release for advancing the treatment of malignant tumors.


Doxorubicin , Drug Liberation , Indocyanine Green , Indoles , Manganese Compounds , Oxides , Photochemotherapy , Photosensitizing Agents , Polymers , Photochemotherapy/methods , Doxorubicin/chemistry , Doxorubicin/pharmacology , Doxorubicin/administration & dosage , Indocyanine Green/chemistry , Indoles/chemistry , Animals , Manganese Compounds/chemistry , Humans , Polymers/chemistry , Cell Line, Tumor , Oxides/chemistry , Photosensitizing Agents/chemistry , Silicon Dioxide/chemistry , Mice , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Neoplasms/drug therapy , Reactive Oxygen Species/metabolism , Drug Delivery Systems , Nanoparticles/chemistry , Drug Carriers/chemistry , Porosity
11.
J Biomed Mater Res B Appl Biomater ; 112(5): e35405, 2024 May.
Article En | MEDLINE | ID: mdl-38701384

The structure and handling properties of a P407 hydrogel-based bone substitute material (BSM) might be affected by different poloxamer P407 and silicon dioxide (SiO2) concentrations. The study aimed to compare the mechanical properties and biological parameters (bone remodeling, BSM degradation) of a hydroxyapatite: silica (HA)-based BSM with various P407 hydrogels in vitro and in an in vivo rat model. Rheological analyses for mechanical properties were performed on one BSM with an SiO2-enriched hydrogel (SPH25) as well on two BSMs with unaltered hydrogels in different gel concentrations (PH25 and PH30). Furthermore, the solubility of all BSMs were tested. In addition, 30 male Wistar rats underwent surgical creation of a well-defined bone defect in the tibia. Defects were filled randomly with PH30 (n = 15) or SPH25 (n = 15). Animals were sacrificed after 12 (n = 5 each), 21 (n = 5 each), and 63 days (n = 5 each). Histological evaluation and histomorphometrical quantification of new bone formation (NB;%), residual BSM (rBSM;%), and soft tissue (ST;%) was conducted. Rheological tests showed an increased viscosity and lower solubility of SPH when compared with the other hydrogels. Histomorphometric analyses in cancellous bone showed a decrease of ST in PH30 (p = .003) and an increase of NB (PH30: p = .001; SPH: p = .014) over time. A comparison of both BSMs revealed no significant differences. The addition of SiO2 to a P407 hydrogel-based hydroxyapatite BSM improves its mechanical stability (viscosity, solubility) while showing similar in vivo healing properties compared to PH30. Additionally, the SiO2-enrichment allows a reduction of poloxamer ratio in the hydrogel without impairing the material properties.


Bone Substitutes , Durapatite , Hydrogels , Poloxamer , Rats, Wistar , Silicon Dioxide , Animals , Male , Poloxamer/chemistry , Poloxamer/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Durapatite/chemistry , Durapatite/pharmacology , Silicon Dioxide/chemistry , Bone Substitutes/chemistry , Bone Substitutes/pharmacology , Rats , Materials Testing , Rheology , Tibia/metabolism
12.
Hum Vaccin Immunother ; 20(1): 2346390, 2024 Dec 31.
Article En | MEDLINE | ID: mdl-38691025

Middle East respiratory coronavirus (MERS-CoV) is a newly emergent, highly pathogenic coronavirus that is associated with 34% mortality rate. MERS-CoV remains listed as priority pathogen by the WHO. Since its discovery in 2012 and despite the efforts to develop coronaviruses vaccines to fight against SARS-CoV-2, there are currently no MERS-CoV vaccine that has been approved. Therefore, there is high demand to continue on the development of prophylactic vaccines against MERS-CoV. Current advancements in vaccine developments can be adapted for the development of improved MERS-CoV vaccines candidates. Nucleic acid-based vaccines, including pDNA and mRNA, are relatively new class of vaccine platforms. In this work, we developed pDNA and mRNA vaccine candidates expressing S.FL gene of MERS-CoV. Further, we synthesized a silane functionalized hierarchical aluminosilicate to encapsulate each vaccine candidates. We tested the nucleic acid vaccine candidates in mice and evaluated humoral antibodies response. Interestingly, we determined that the non-encapsulated, codon optimized S.FL pDNA vaccine candidate elicited the highest level of antibody responses against S.FL and S1 of MERS-CoV. Encapsulation of mRNA with nanoporous aluminosilicate increased the humoral antibody responses, whereas encapsulation of pDNA did not. These findings suggests that MERS-CoV S.FL pDNA vaccine candidate induced the highest level of humoral responses. This study will enhance further optimization of nanosilica as potential carrier for mRNA vaccines. In conclusion, this study suggests MERS-CoV pDNA vaccine candidate as a suitable vaccine platform for further pivotal preclinical testings.


Antibodies, Viral , Coronavirus Infections , Middle East Respiratory Syndrome Coronavirus , Nanoparticles , Silicon Dioxide , Vaccines, DNA , Viral Vaccines , Animals , Vaccines, DNA/immunology , Vaccines, DNA/genetics , Vaccines, DNA/administration & dosage , Middle East Respiratory Syndrome Coronavirus/immunology , Middle East Respiratory Syndrome Coronavirus/genetics , Mice , Viral Vaccines/immunology , Viral Vaccines/genetics , Viral Vaccines/administration & dosage , Antibodies, Viral/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/immunology , Silicon Dioxide/chemistry , Mice, Inbred BALB C , Female , Humans , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/genetics , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Vaccine Development
13.
Part Fibre Toxicol ; 21(1): 23, 2024 May 11.
Article En | MEDLINE | ID: mdl-38734694

BACKGROUND: Inhalation of biopersistent fibers like asbestos can cause strong chronic inflammatory effects, often resulting in fibrosis or even cancer. The interplay between fiber shape, fiber size and the resulting biological effects is still poorly understood due to the lack of reference materials. RESULTS: We investigated how length, diameter, aspect ratio, and shape of synthetic silica fibers influence inflammatory effects at doses up to 250 µg cm-2. Silica nanofibers were prepared with different diameter and shape. Straight (length ca. 6 to 8 µm, thickness ca. 0.25 to 0.35 µm, aspect ratio ca. 17:1 to 32:1) and curly fibers (length ca. 9 µm, thickness ca. 0.13 µm, radius of curvature ca. 0.5 µm, aspect ratio ca. 70:1) were dispersed in water with no apparent change in the fiber shape during up to 28 days. Upon immersion in aqueous saline (DPBS), the fibers released about 5 wt% silica after 7 days irrespectively of their shape. The uptake of the fibers by macrophages (human THP-1 and rat NR8383) was studied by scanning electron microscopy and confocal laser scanning microscopy. Some fibers were completely taken up whereas others were only partially internalized, leading to visual damage of the cell wall. The biological effects were assessed by determining cell toxicity, particle-induced chemotaxis, and the induction of gene expression of inflammatory mediators. CONCLUSIONS: Straight fibers were only slightly cytotoxic and caused weak cell migration, regardless of their thickness, while the curly fibers were more toxic and caused significantly stronger chemotaxis. Curly fibers also had the strongest effect on the expression of cytokines and chemokines. This may be due to the different aspect ratio or its twisted shape.


Chemotaxis , Macrophages , Particle Size , Silicon Dioxide , Silicon Dioxide/toxicity , Silicon Dioxide/chemistry , Animals , Humans , Rats , Macrophages/drug effects , Macrophages/metabolism , Chemotaxis/drug effects , Nanofibers/toxicity , Nanofibers/chemistry , THP-1 Cells , Transcriptome/drug effects , Mineral Fibers/toxicity , Cytokines/metabolism , Cytokines/genetics , Cell Line
14.
J Chromatogr A ; 1725: 464943, 2024 Jun 21.
Article En | MEDLINE | ID: mdl-38691924

In this study, we proposed a novel method utilizing polyethyleneimine (PEI)-modified halloysite nanotubes (HNTs)-based hybrid silica monolithic spin tip to analyze hydrophilic ß-lactam antibiotics and ß-lactamases inhibitors in whole blood samples for the first time. HNTs were incorporated directly into the hybrid silica monolith via a sol-gel method, which improved the hydrophilicity of the matrix. The as-prepared monolith was further modified with PEI by glutaraldehyde coupling reaction. It was found that the PEI-modified HNTs-based hybrid silica monolith enabled a large adsorption capacity of cefoperazone at 35.7 mg g-1. The monolithic spin tip-based purification method greatly reduced the matrix effect of whole blood samples and had a detection limit as low as 0.1 - 0.2 ng mL-1. In addition, the spiked recoveries of sulbactam, cefuroxime, and cefoperazone in blank whole blood were in the range of 89.3-105.4 % for intra-day and 90.6-103.5 % for inter-day, with low relative standard deviations of 1.3-7.2 % and 4.9-10.5 %, respectively. This study introduces a new strategy for preparing nanoparticles incorporated in a hybrid silica monolith with a high adsorption capacity. Moreover, it offers a valuable tool to monitor sulbactam, cefoperazone, and cefuroxime in whole blood from pregnant women with the final aim of guiding their administration.


Cefoperazone , Cefuroxime , Hydrophobic and Hydrophilic Interactions , Limit of Detection , Nanotubes , Silicon Dioxide , Solid Phase Extraction , Sulbactam , Cefoperazone/blood , Cefoperazone/chemistry , Humans , Sulbactam/blood , Sulbactam/chemistry , Solid Phase Extraction/methods , Silicon Dioxide/chemistry , Nanotubes/chemistry , Cefuroxime/blood , Cefuroxime/chemistry , Clay/chemistry , Adsorption , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/chemistry , Polyethyleneimine/chemistry , Chromatography, High Pressure Liquid/methods , Reproducibility of Results
15.
Anal Chem ; 96(19): 7470-7478, 2024 May 14.
Article En | MEDLINE | ID: mdl-38696229

MicroRNAs (miRNAs) are endogenous and noncoding single-stranded RNA molecules with a length of approximately 18-25 nucleotides, which play an undeniable role in early cancer screening. Therefore, it is very important to develop an ultrasensitive and highly specific method for detecting miRNAs. Here, we present a bottom-up assembly approach for modifying glass microtubes with silica nanowires (SiNWs) and develop a label-free sensing platform for miRNA-21 detection. The three-dimensional (3D) networks formed by SiNWs make them abundant and highly accessible sites for binding with peptide nucleic acid (PNA). As a receptor, PNA has no phosphate groups and exhibits an overall electrically neutral state, resulting in a relatively small repulsion between PNA and RNA, which can improve the hybridization efficiency. The SiNWs-filled glass microtube (SiNWs@GMT) sensor enables ultrasensitive, label-free detection of miRNA-21 with a detection limit as low as 1 aM at a detection range of 1 aM-100 nM. Noteworthy, the sensor can still detect miRNA-21 in the range of 102-108 fM in complex solutions containing 1000-fold homologous interference of miRNAs. The high anti-interference performance of the sensor enables it to specifically recognize target miRNA-21 in the presence of other miRNAs and distinguish 1-, 3-mismatch nucleotide sequences. Significantly, the sensor platform is able to detect miRNA-21 in the lysate of breast cancer cell lines (e.g., MCF-7 cells and MDA-MB-231 cells), indicating that it has good potential in the screening of early breast cancers.


Glass , MicroRNAs , Nanowires , Peptide Nucleic Acids , Silicon Dioxide , MicroRNAs/analysis , Peptide Nucleic Acids/chemistry , Silicon Dioxide/chemistry , Humans , Nanowires/chemistry , Glass/chemistry , Biosensing Techniques/methods , Limit of Detection
16.
Anal Chem ; 96(19): 7679-7686, 2024 May 14.
Article En | MEDLINE | ID: mdl-38698534

Despite the success of surface-enhanced Raman spectroscopy (SERS) for detecting DNA immobilized on plasmonic metal surfaces, its quantitative response is limited by the rapid falloff of enhancement with distance from the metal surface and variations in sensitivity that depend on orientation and proximity to plasmonic "hot spots". In this work, we assess an alternative approach for enhancing detection by immobilizing DNA on the interior surfaces of porous silica particles. These substrates provide over a 1000-fold greater surface area for detection compared to a planar support. The porous silica substrate is a purely dielectric material with randomly oriented internal surfaces, where scattering is independent of proximity and orientation of oligonucleotides relative to the silica surface. We characterize the quantitative response of Raman scattering from DNA in porous silica particles with sequences used in previous SERS investigations of DNA for comparison. The results show that Raman scattering of DNA in porous silica is independent of distance of nucleotides from the silica surface, allowing detection of longer DNA strands with constant sensitivity. The surface area enhancement within particles is reproducible (<4% particle-to-particle variation) owing to the uniform internal pore structure and surface chemistry of the silica support. DNA immobilization with a bis-thiosuccinimide linker provides a Raman-active internal standard for quantitative interpretation of Raman scattering results. Despite the high (30 mM) concentrations of immobilized DNA within porous silica particles, they can be used to measure nanomolar binding affinities of target molecules to DNA by equilibrating a very small number of particles with a sufficiently large volume of low-concentration solution of target molecules.


DNA , Silicon Dioxide , Spectrum Analysis, Raman , Surface Properties , Silicon Dioxide/chemistry , Spectrum Analysis, Raman/methods , Porosity , DNA/chemistry , DNA/analysis
17.
Biomacromolecules ; 25(5): 2990-3000, 2024 May 13.
Article En | MEDLINE | ID: mdl-38696732

Recently, we reported the synthesis of a hydrophilic aldehyde-functional methacrylic polymer (Angew. Chem., 2021, 60, 12032-12037). Herein we demonstrate that such polymers can be reacted with arginine in aqueous solution to produce arginine-functional methacrylic polymers without recourse to protecting group chemistry. Careful control of the solution pH is essential to ensure regioselective imine bond formation; subsequent reductive amination leads to a hydrolytically stable amide linkage. This new protocol was used to prepare a series of arginine-functionalized diblock copolymer nanoparticles of varying size via polymerization-induced self-assembly in aqueous media. Adsorption of these cationic nanoparticles onto silica was monitored using a quartz crystal microbalance. Strong electrostatic adsorption occurred at pH 7 (Γ = 14.7 mg m-2), whereas much weaker adsorption occurred at pH 3 (Γ = 1.9 mg m-2). These findings were corroborated by electron microscopy, which indicated a surface coverage of 42% at pH 7 but only 5% at pH 3.


Arginine , Nanoparticles , Nanoparticles/chemistry , Adsorption , Arginine/chemistry , Hydrogen-Ion Concentration , Polymerization , Silicon Dioxide/chemistry , Polymers/chemistry , Polymethacrylic Acids/chemistry , Polymethacrylic Acids/chemical synthesis
18.
Mikrochim Acta ; 191(6): 326, 2024 05 13.
Article En | MEDLINE | ID: mdl-38740583

Migration is an initial step in tumor expansion and metastasis; suppressing cellular migration is beneficial to cancer therapy. Herein, we designed a novel biogated nanoagents that integrated the migration inhibitory factor into the mesoporous silica nanoparticle (MSN) drug delivery nanosystem to realize cell migratory inhibition and synergistic treatment. Antisense oligonucleotides (Anti) of microRNA-330-3p, which is positively related with cancer cell proliferation, migration, invasion, and angiogenesis, not only acted as the locker for blocking drugs but also acted as the inhibitory factor for suppressing migration via gene therapy. Synergistic with gene therapy, the biogated nanoagents (termed as MSNs-Gef-Anti) could achieve on-demand drug release based on the intracellular stimulus-recognition and effectively kill tumor cells. Experimental results synchronously demonstrated that the migration suppression ability of MSNs-Gef-Anti nanoagents (nearly 30%) significantly contributed to cancer therapy, and the lethality rate of the non-small-cell lung cancer was up to 70%. This strategy opens avenues for realizing efficacious cancer therapy and should provide an innovative way for pursuing the rational design of advanced nano-therapeutic platforms with the combination of cancer cell migratory inhibition.


Cell Movement , MicroRNAs , Nanoparticles , Silicon Dioxide , Silicon Dioxide/chemistry , Humans , Cell Movement/drug effects , Porosity , Nanoparticles/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Oligonucleotides, Antisense/chemistry , Oligonucleotides, Antisense/pharmacology , Animals , Cell Line, Tumor , Drug Carriers/chemistry , Cell Proliferation/drug effects , Mice , Genetic Therapy/methods , A549 Cells
19.
Mikrochim Acta ; 191(5): 285, 2024 04 23.
Article En | MEDLINE | ID: mdl-38652174

One significant constraint in the advancement of biosensors is the signal-to-noise ratio, which is adversely affected by the presence of interfering factors such as blood in the sample matrix. In the present investigation, a specific aptamer binding was chosen for its affinity, while exhibiting no binding affinity towards non-target bacterial cells. This selective binding property was leveraged to facilitate the production of magnetic microparticles decorated with aptamers. A novel assay was developed to effectively isolate S. pneumoniae from PBS or directly from blood samples using an aptamer with an affinity constant of 72.8 nM. The capture experiments demonstrated efficiencies up to 87% and 66% are achievable for isolating spiked S. pneumoniae in 1 mL PBS and blood samples, respectively.


Aptamers, Nucleotide , Silicon Dioxide , Aptamers, Nucleotide/chemistry , Silicon Dioxide/chemistry , Streptococcus pneumoniae/isolation & purification , Streptococcus pneumoniae/chemistry , Humans , Biosensing Techniques/methods , Magnetite Nanoparticles/chemistry
20.
Biomed Mater ; 19(4)2024 May 13.
Article En | MEDLINE | ID: mdl-38688293

Collagen type I is a material widely used for 3D cell culture and tissue engineering. Different architectures, such as gels, sponges, membranes, and nanofibers, can be fabricated with it. In collagen hydrogels, the formation of fibrils and fibers depends on various parameters, such as the source of collagen, pH, temperature, concentration, age, etc. In this work, we study the fibrillogenesis process in collagen type I hydrogels with different types of microbeads embedded, using optical techniques such as turbidity assay and confocal reflectance microscopy. We observe that microbeads embedded in the collagen matrix hydrogels modify the fibrillogenesis. Our results show that carboxylated fluorescent microbeads accelerate 3.6 times the gelation, while silica microbeads slow down the formation of collagen fibrils by a factor of 1.9, both compared to pure collagen hydrogels. Our observations suggest that carboxylate microbeads act as nucleation sites and the early collagen fibrils bind to the microbeads.


Collagen Type I , Hydrogels , Microspheres , Hydrogels/chemistry , Collagen Type I/chemistry , Animals , Collagen/chemistry , Tissue Engineering/methods , Hydrogen-Ion Concentration , Biocompatible Materials/chemistry , Silicon Dioxide/chemistry , Microscopy, Confocal , Temperature , Carboxylic Acids/chemistry , Materials Testing
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