Effects of Different Surface Functionalizations of Silica Nanoparticles on Mesenchymal Stem Cells.

Physicochemical properties of nanoparticles, such as particle size, surface charge, and particle shape, have a significant impact on cell activities. However, the effects of surface functionalization of nanoparticles with small chemical groups on stem cell behavior and function remain understudied. Herein, we incorporated different chemical functional groups (amino, DETA, hydroxyl, phosphate, and sulfonate with charges of +9.5, + 21.7, -14.1, -25.6, and -37.7, respectively) to the surface of inorganic silica nanoparticles. To trace their effects on mesenchymal stem cells (MSCs) of rat bone marrow, these functionalized silica nanoparticles were used to encapsulate Rhodamine B fluorophore dye. We found that surface functionalization with positively charged and short-chain chemical groups facilitates cell internalization and retention of nanoparticles in MSCs. The endocytic pathway differed among functionalized nanoparticles when tested with ion-channel inhibitors. Negatively charged nanoparticles mainly use lysosomal exocytosis to exit cells, while positively charged nanoparticles can undergo endosomal escape to avoid scavenging. The cytotoxic profiles of these functionalized silica nanoparticles are still within acceptable limits and tolerable. They exerted subtle effects on the actin cytoskeleton and migration ability. Last, phosphate-functionalized nanoparticles upregulate osteogenesis-related genes and induce osteoblast-like morphology, implying that it can direct MSCs lineage specification for bone tissue engineering. Our study provides insights into the rational design of biomaterials for effective drug delivery and regenerative medicine.

Composite Aerogel Scaffolds Containing Flexible Silica Nanofiber and Tricalcium Phosphate Enable Skin Regeneration.

Poor hemostatic ability and less vascularization at the injury site could hinder wound healing as well as adversely affect the quality of life (QOL). An ideal wound dressing should exhibit certain characteristics: (a) good hemostatic ability, (b) rapid wound healing, and (c) skin appendage formation. This necessitates the advent of innovative dressings to facilitate skin regeneration. Therapeutic ions, such as silicon ions (Si4+) and calcium ions (Ca2+), have been shown to assist in wound repair. The Si4+ released from silica (SiO2) can upregulate the expression of proteins, including the vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA), which is conducive to vascularization; Ca2+ released from tricalcium phosphate (TCP) can promote the coagulation alongside upregulating the expression of cell migration and cell differentiation related proteins, thereby facilitating the wound repair. The overarching objective of this study was to exploit short SiO2 nanofibers along with the TCP to prepare TCPx@SSF aerogels and assess their wound healing ability. Short SiO2 nanofibers were prepared by electrospinning and blended with varying proportions of TCP to afford TCPx@SSF aerogel scaffolds. The TCPx@SSF aerogels exhibited good cytocompatibility in a subcutaneous implantation model and manifested a rapid hemostatic effect (hemostatic time 75 s) in a liver trauma model in the rabbit. These aerogel scaffolds also promoted skin regeneration and exhibited rapid wound closure, epithelial tissue regeneration, and collagen deposition. Taken together, TCPx@SSF aerogels may be valuable for wound healing.

Exploring the mechanism underlying the antifungal activity of chitosan-based ZnO, CuO, and SiO2 nanocomposites as nanopesticides against Fusarium solani and Alternaria solani.

Chitosan-based nanocomposites (CS NCs) are gaining considerable attention as multifaceted antifungal agents. This study investigated the antifungal activity of NCs against two phytopathogenic strains: Fusarium solani (F. solani) and Alternaria solani (A. solani). Moreover, it sheds light on their underlying mechanisms of action. The NCs, CS-ZnO, CS-CuO, and CS-SiO2, were characterized using advanced methods. Dynamic and electrophoretic light scattering techniques revealed their size range (60-170 nm) and cationic nature, as indicated by the positive zeta potential values (from +16 to +22 mV). Transmission electron microscopy revealed the morphology of the NCs as agglomerates formed between the chitosan and oxide components. X-ray diffraction patterns confirmed crystalline structures with specific peaks indicating their constituents. Antifungal assessments using the agar diffusion technique demonstrated significant inhibitory effects of the NCs on both fungal strains (1.5 to 4-fold), surpassing the performance of the positive control, nystatin. Notably, the NCs exhibited superior antifungal potency, with CS-ZnO NCs being the most effective. A. solani was the most sensitive strain to the studied agents. Furthermore, the tested NCs induced oxidative stress in fungal cells, which elevated stress biomarker levels, such as superoxide dismutase (SOD) activity and protein carbonyl content (PCC), 2.5 and 6-fold for the most active CS-CuO in F. solani respectively. Additionally, they triggered membrane lipid peroxidation up to 3-fold higher compared to control, a process that potentially compromises membrane integrity. Laurdan fluorescence spectroscopy highlighted alterations in the molecular organization of fungal cell membranes induced by the NCs. CS-CuO NCs induced a membrane rigidifying effect, while CS-SiO2 and CS-ZnO could rigidify membranes in A. solani and fluidize them in F. solani. In summary, this study provides an in-depth understanding of the interactions of CS-based NCs with two fungal strains, showing their antifungal activity and offering insights into their mechanisms of action. These findings emphasize the potential of these NCs as effective and versatile antifungal agents.

Immunogenic Cell Death Induction and Oxygenation by Multifunctional Hollow Silica/Copper-Doped Carbon Dots.

The metastasis and recurrence of cancer are related to immunosuppression and hypoxia in the tumor microenvironment. Activating immune activity and improving the hypoxic environment face essential challenges. This paper reports on a multifunctional nanomaterial, HSCCMBC, that induces immunogenic cell death through powerful photodynamic therapy/chemodynamic therapy synergistic antitumor effects. The tumor microenvironment changed from the immunosuppressive type to immune type, activated the immune activity of the system, decomposed hydrogen peroxide to generate oxygen based on Fenton-like reaction, and effectively increased the level of intracellular O2 with the assistance of 3-bromopyruvate, a cell respiratory inhibitor. The structure and composition of HSCCMBC were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, infrared spectroscopy, etc. Oxygen probe RDPP was used to investigate the oxygen level inside and outside the cell, and hydroxyl radical probe tetramethylbenzidine was used to investigate the Fenton-like reaction ability. The immunofluorescence method investigated the expression of various immune markers and hypoxia-inducing factors in vitro and in vivo after treatment. In vitro and in vivo experiments indicate that HSCCMBC is an excellent antitumor agent and is expected to be a candidate drug for antitumor immunotherapy.

Preparation of mesoporous silica/hydroxyapatite loaded quercetin nanoparticles and research on its antibacterial properties.

In this study, amino-functionalized mesoporous silica/hydroxyapatite nanoparticles (MSNS/HAP) with the property of acid dissociation have been prepared as a traditional Chinese medicine monomer carriers to improve the drug loading rate and antibacterial properties of antimicrobial quercetin (QUE) in vitro. The experimental results confirm that the drug loading rate of MSNs/HAP is 28.94 %, which is about 3.6 times higher than that of aminated mesoporous sililca nanoparticles (MSNs). The drug release of QUE on MSNs/HAP is pH-sensitive in phosphate buffered saline (pH=4.0-7.4). The above fabricated traditional Chinese medicine monomer modified nanocomposites (QUE@MSNs/HAP) displays concentration-dependent inhibitory effect, which shows better antibacterial effect than free QUE. The minimum inhibitory concentration for two tested bacteria, Staphylococcus aureus (S.aureus) and Escherichia coli (E.coli), is 256 mg·L -1. In summary, QUE@MSNs/HAP have successfully prepared, which not only improves the bio-availability of QUE, but also has acid-sensitive drug release properties. Compared with free QUE, its antibacterial performance significantly enhances, which provides a theoretical basis for the application of Chinese medicine molecules in bacterial treatment.

Effect of the Photoreduction Process on the Self-Cleaning and Antibacterial Activity of Au-Doped TiO2 Colloids on Cotton Fabric.

This study aims at understanding the effect of the photoreduction process during the synthesis of gold (Au)-doped TiO2 colloids on the conferred functionalities on cotton fabrics. TiO2/Au and TiO2/Au/SiO2 colloids were synthesized through the sol-gel method with and without undergoing the photoreduction step based on different molar ratios of Au:Ti (0.001 and 0.01) and TiO2/SiO2 (1:1 and 1:2.3). The colloids were applied to cotton fabrics, and the obtained photocatalytic self-cleaning, wet photocatalytic activity, UV protection, and antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria were investigated. The obtained results demonstrated that the photoreduction of Au weakened the self-cleaning effect and reduced the photocatalytic activity of coated fabrics. Also, an excess amount of Au deteriorated the photocatalytic activity under both UV and visible light. The most efficient self-cleaning effect was obtained on fabrics coated with a ternary TiO2/Au/SiO2 colloid containing ionic Au, where it decomposed coffee and red-wine stains after 3 h of illumination. Adding silica (SiO2) made the fabrics superhydrophilic and led to greater methylene blue (MB) dye adsorption, a faster dye degradation pace, and more efficient stain removal. Moreover, the photoreduction process affected the size of Au nanoparticles (NPs), weakened the antibacterial activity of fabrics against both types of tested bacteria, and modestly increased the UV protection. In general, the photoactivity of Au-doped colloids was influenced by the synthesis method, the ionic and metallic states of the Au dopant, the concentration of the Au dopant, and the presence and concentration of silica.

Remarkable enhancement of cinnamaldehyde antimicrobial activity encapsulated in capped mesoporous nanoparticles: A new "nanokiller" approach in the era of antimicrobial resistance.

Combating antimicrobial resistance is one of the biggest health challenges because of the ineffectiveness of standard biocide treatments. This challenge could be approached using natural products, which have demonstrated powerful therapeutics against multidrug-resistant microbes. In the present work, a nanodevice consisting of mesoporous silica nanoparticles loaded with an essential oil component (cinnamaldehyde) and functionalized with the polypeptide ε-poly-l-lysine is developed and used as an antimicrobial agent. In the presence of the corresponding stimuli (i.e., exogenous proteolytic enzymes from bacteria or fungi), the polypeptide is hydrolyzed, and the cinnamaldehyde delivery is enhanced. The nanodevice's release mechanism and efficacy are evaluated in vitro against the pathogenic microorganisms Escherichia coli, Staphylococcus aureus, and Candida albicans. The results demonstrate that the new device increases the delivery of the cinnamaldehyde via a biocontrolled uncapping mechanism triggered by proteolytic enzymes. Moreover, the nanodevice notably improves the antimicrobial efficacy of cinnamaldehyde when compared to the free compound, ca. 52-fold for E. coli, ca. 60-fold for S. aureus, and ca. 7-fold for C. albicans. The enhancement of the antimicrobial activity of the essential oil component is attributed to the decrease of its volatility due to its encapsulation in the porous silica matrix and the increase of its local concentration when released due to the presence of microorganisms.

A composite hydrogel loaded with the processed pyritum promotes bone repair via stimulate the osteogenic differentiation of BMSCs.

Tissue engineering shows promise in repairing extensive bone defects. The promotion of proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by biological scaffolds has a significant impact on bone regeneration outcomes. In this study we used an injectable hydrogel, known as aminated mesoporous silica gel composite hydrogel (MSNs-NH2@GelMA), loaded with a natural drug, processed pyritum (PP), to promote healing of bone defects. The mechanical properties of the composite hydrogel were significantly superior to those of the blank hydrogel. In vitro experiments revealed that the composite hydrogel stimulated the osteogenic differentiation of BMSCs, and significantly increased the expression of type I collagen (Col 1), runt-related transcription factor 2 (Runx 2), alkaline phosphatase (ALP), osteocalcin (OCN). In vivo experiments showed that the composite hydrogel promoted the generation of new bones. These findings provide evidence that the composite hydrogel pyritum-loaded holds promise as a biomaterial for bone repair.

Lethal puncturing of planktonic Gram-positive and Gram-negative bacteria by magnetically-rotated silica hexapods.

Planktonic bacterial presence in many industrial and environmental applications and personal health-care products is generally countered using antimicrobials. However, antimicrobial chemicals present an environmental threat, while emerging resistance reduces their efficacy. Suspended bacteria have no defense against mechanical attack. Therefore, we synthesized silica hexapods on an α-Fe2O3 core that can be magnetically-rotated to inflict lethal cell-wall-damage to planktonic Gram-negative and Gram-positive bacteria. Hexapods possessed 600 nm long nano-spikes, composed of SiO2, as shown by FTIR and XPS. Fluorescence staining revealed cell wall damage caused by rotating hexapods. This damage was accompanied by DNA/protein release and bacterial death that increased with increasing rotational frequency up to 500 rpm. Lethal puncturing was more extensive on Gram-negative bacteria than on Gram-positive bacteria, which have a thicker peptidoglycan layer with a higher Young's modulus. Simulations confirmed that cell-wall-puncturing occurs at lower nano-spike penetration levels in the cell walls of Gram-negative bacteria. This approach offers a new way to kill bacteria in suspension, not based on antimicrobial chemicals.

Bioinspired superhydrophobic surfaces with silver and nitric oxide-releasing capabilities to prevent device-associated infections and thrombosis.

Bacteria-associated infections and thrombus formation are the two major complications plaguing the application of blood-contacting medical devices. Therefore, functionalized surfaces and drug delivery for passive and active antifouling strategies have been employed. Herein, we report the novel integration of bio-inspired superhydrophobicity with nitric oxide release to obtain a functional polymeric material with anti-thrombogenic and antimicrobial characteristics. The nitric oxide release acts as an antimicrobial agent and platelet inhibitor, while the superhydrophobic components prevent non-specific biofouling. Widely used medical-grade silicone rubber (SR) substrates that are known to be susceptible to biofilm and thrombus formation were dip-coated with fluorinated silicon dioxide (SiO2) and silver (Ag) nanoparticles (NPs) using an adhesive polymer as a binder. Thereafter, the resulting superhydrophobic (SH) SR substrates were impregnated with S-nitroso-N-acetylpenicillamine (SNAP, an NO donor) to obtain a superhydrophobic, Ag-bound, NO-releasing (SH-SiAgNO) surface. The SH-SiAgNO surfaces had the lowest amount of viable adhered E. coli (> 99.9 % reduction), S. aureus (> 99.8 % reduction), and platelets (> 96.1 % reduction) as compared to controls while demonstrating no cytotoxic effects on fibroblast cells. Thus, this innovative approach is the first to combine SNAP with an antifouling SH polymer surface that possesses the immense potential to minimize medical device-associated complications without using conventional systemic anticoagulation and antibiotic treatments.

Injectable and In Situ Formed Dual-Network Hydrogel Reinforced by Mesoporous Silica Nanoparticles and Loaded with BMP-4 for the Closure and Repair of Skull Defects.

Bone defects are a common and challenging orthopedic problem with poor self-healing ability and long treatment cycles. The difficult-to-heal bone defects cause a significant burden of medical expenses on patients. Currently, biomaterials with mechanical stability, long-lasting action, and osteogenic activity are considered as a suitable way to effectively heal bone defects. Here, an injectable double network (DN) hydrogel prepared using physical and chemical cross-linking methods is designed. The first rigid network is constructed using methylpropenylated hyaluronic acid (HAMA), while the addition of chitosan oligosaccharide (COS) forms a second flexible network by physical cross-linking. The mesoporous silica nanoparticles (MSN) loaded with bone morphogenetic protein-4 (BMP-4) were embedded into DN hydrogel, which not only enhanced the mechanical stability of the hydrogel, but also slowly released BMP-4 to achieve long-term skull repair. The designed composite hydrogel showed an excellent compression property and deformation resistance. In vitro studies confirmed that the HAMA/COS/MSN@BMP-4 hydrogel had good biocompatibility and showed great potential in supporting proliferation and osteogenic differentiation of mouse embryo osteoblast precursor (MC3T3-E1) cells. Furthermore, in vivo studies confirmed that the DN hydrogel successfully filled and closed irregular skull defect wounds, effectively promoted bone regeneration, and significantly promoted bone repair compared with the control group. In addition, HAMA/COS/MSN@BMP-4 hydrogel precursor solution can quickly form hydrogel in situ at the wound by ultraviolet light, which can be applied to the closure and repair of wounds of different shapes, which provides the new way for the treatment of bone defects.

Promoting bond durability by a novel fabricated bioactive dentin adhesive.

OBJECTIVE: To prepare a bioactive dentin adhesive and investigate its effect on promoting bonding durability of dentin. METHODS: The mineralization of the bioactive glass with high phosphorus (10.8 mol% P2O5-54.2 mol% SiO2-35 mol% CaO, named PSC) and its ability to induce type I collagen mineralization were observed by SEM and TEM. The Control-Bond and the bioactive dentin adhesive containing 20 wt% PSC particles (PSC-Bond) were prepared, and their degree of conversion (DC), microtensile bond strength (µTBS), film thickness and mineralization performance were evaluated. To evaluate the bonding durability, dentin bonding samples were prepared by Control-Bond and PSC-Bond, and mineralizated in simulated body fluid for 24 h, 3 months, and 6 months. Then, the long-term bond strength and microleakage at the adhesive interface of dentin bonding samples were evaluated by microtensile testing and semiquantitative ELIASA respectively. RESULTS: The PSC showed superior mineralization at 24 h and induced type I collagen mineralization to some extent under weakly alkaline conditions. For PSC-Bond, DC was 62.65 ± 1.20%, µTBS was 39.25 ± 4.24 MPa and film thickness was 17.00 ± 2.61 µm. PSC-Bond also formed hydroxyapatite and maintained good mineralization at the bonding interface. At 24 h, no significant differences in µTBS and interface microleakage were observed between the Control-Bond and PSC-Bond groups. After 6 months of aging, the µTBS was significantly higher and the interface microleakage was significantly lower of PSC-Bond group than those of Control-Bond group. SIGNIFICANCE: PSC-Bond maintained bond strength stability and reduced interface microleakage to some extent, possibly reducing the occurrence of secondary caries, while maintaining long-term effectiveness of adhesive restorations.

Novel silicene-mesoporous silica nanoparticles conjugated gemcitabine induced cellular apoptosis via upregulating NF-κB p65 nuclear translocation suppresses pancreatic cancer growthin vitroandin vivo.

Pancreatic cancer's high fatality rates stem from its resistance to systemic drug delivery and aggressive metastasis, limiting the efficacy of conventional treatments. In this study, two-dimensional ultrathin silicene nanosheets were initially synthesized and near-infrared-responsive two-dimensional silicene-mesoporous silica nanoparticles (SMSNs) were successfully constructed to load the clinically-approved conventional pancreatic cancer chemotherapeutic drug gemcitabine. Experiments on nanoparticle characterization show that they have excellent photothermal conversion ability and stability. Then silicene-mesoporous silica nanoparticles loaded with gemcitabine nanoparticles (SMSN@G NPs) were employed in localized photothermal therapy to control pancreatic tumor growth and achieve therapeutic effects. Our research confirmed the functionality of SMSN@G NPs through immunoblotting and apoptotic assays, demonstrating its capacity to enhance the nuclear translocation of the NF-κB p65, further affect the protein levels of apoptosis-related genes, induce the apoptosis of tumor cells, and ultimately inhibit the growth of the tumor. Additionally, the study assessed the inhibitory role of SMSN@G NPs on pancreatic neoplasm growthin vivo, revealing its excellent biocompatibility. SMSN@G NPs have a nice application prospect for anti-pancreatic tumors.

A novel microglia-targeting strategy based on nanoparticle-mediated delivery of miR-26a-5p for long-lasting analgesia in chronic pain.

Accumulating evidence supports the notion that microglia play versatile roles in different chronic pain conditions. However, therapeutic strategies of chronic pain by targeting microglia remain largely overlooked. This study seeks to develop a miRNA-loaded nano-delivery system by targeting microglia, which could provide a decent and long-lasting analgesia for chronic pain. Surface aminated mesoporous silica nanoparticles were adopted to load miR-26a-5p, a potent analgesic miRNA, by electrostatic adsorption, which can avoid miR-26a-5p is rapidly released and degraded. Then, targeting peptide MG1 was modified on the surface of aminated mesoporous silica particles for microglia targeting. In peripheral nerve injury induced neuropathic pain model, a satisfactory anti-allodynia effect with about 6 weeks pain-relief duration were achieved through targeting microglia strategy, which decreased microglia activation and inflammation by Wnt5a, a non-canonical Wnt pathway. In inflammatory pain and chemotherapy induced peripheral neuropathic pain, microglia targeting strategy also exhibited more efficient analgesia and longer pain-relief duration than others. Overall, we developed a microglia-targeting nano-delivery system, which facilitates precisely miR-26a-5p delivery to enhance analgesic effect and duration for several chronic pain conditions.

Bionic Nanocoating of Prosthetic Grafts Significantly Reduces Bacterial Growth.

Prosthetic materials are a source of bacterial infections, with significant morbidity and mortality. Utilizing the bionic "Lotus effect," we generated superhydrophobic vascular prostheses by nanocoating and investigated their resistance to bacterial colonization. Nanoparticles were generated from silicon dioxide (SiO2), and coated vascular prostheses developed a nanoscale roughness with superhydrophobic characteristics. Coated grafts and untreated controls were incubated with different bacterial solutions including heparinized blood under mechanical stress and during artificial perfusion and were analyzed. Bioviability- and toxicity analyses of SiO2 nanoparticles were performed. Diameters of SiO2 nanoparticles ranged between 20 and 180 nm. Coated prostheses showed a water contact angle of > 150° (mean 154 ± 3°) and a mean water roll-off angle of 9° ± 2°. Toxicity and viability experiments demonstrated no toxic effects of SiO2 nanoparticles on human induced pluripotent stem cell-derived cardiomyocytes endothelial cells, fibroblasts, and HEK239T cells. After artificial perfusion with a bacterial solution (Luciferase+ Escherichia coli), bioluminescence imaging measurements showed a significant reduction of bacterial colonization of superhydrophobic material-coated prostheses compared to that of untreated controls. At the final measurement (t = 60 min), a 97% reduction of bacterial colonization was observed with superhydrophobic material-coated prostheses. Superhydrophobic vascular prostheses tremendously reduced bacterial growth. During artificial perfusion, the protective superhydrophobic effects of the vascular grafts could be confirmed using bioluminescence imaging.

Antifungal activity of Fe3O4@SiO2/Schiff-base/Cu(II) magnetic nanoparticles against pathogenic Candida species.

The antifungal efficacy and cytotoxicity of a novel nano-antifungal agent, the Fe3O4@SiO2/Schiff-base complex of Cu(II) magnetic nanoparticles (MNPs), have been assessed for targeting drug-resistant Candida species. Due to the rising issue of fungal infections, especially candidiasis, and resistance to traditional antifungals, there is an urgent need for new therapeutic strategies. Utilizing Schiff-base ligands known for their broad-spectrum antimicrobial activity, the Fe3O4@SiO2/Schiff-base/Cu(II) MNPs have been synthesized. The Fe3O4@SiO2/Schiff-base/Cu(II) MNPs was characterized by Fourier Transform-Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), Energy-dispersive X-ray (EDX), Vibrating Sample Magnetometer (VSM), and Thermogravimetric analysis (TGA), demonstrating successful synthesis. The antifungal potential was evaluated against six Candida species (C. dubliniensis, C. krusei, C. tropicalis, C. parapsilosis, C. glabrata, and C. albicans) using the broth microdilution method. The results indicated strong antifungal activity in the range of 8-64 µg/mL with the lowest MIC (8 µg/mL) observed against C. parapsilosis. The result showed the MIC of 32 µg/mL against C. albicans as the most common infection source. The antifungal mechanism is likely due to the disruption of the fungal cell wall and membrane, along with increased reactive oxygen species (ROS) generation leading to cell death. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay for cytotoxicity on mouse L929 fibroblastic cells suggested low toxicity and even enhanced cell proliferation at certain concentrations. This study demonstrates the promise of Fe3O4@SiO2/Schiff-base/Cu(II) MNPs as a potent antifungal agent with potential applications in the treatment of life-threatening fungal infections, healthcare-associated infections, and beyond.

The role of DRP1 mediated mitophagy in HT22 cells apoptosis induced by silica nanoparticles.

Silica nanoparticles (SiNPs) are widely used in the biomedical field and can enter the central nervous system through the blood-brain barrier, causing damage to hippocampal neurons. However, the specific mechanism remains unclear. In this experiment, HT22 cells were selected as the experimental model in vitro, and the survival rate of cells under the action of SiNPs was detected by MTT method, reactive oxygen species (ROS), lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and adenosine triphosphate (ATP) were tested by the kit, the ultrastructure of the cells was observed by transmission electron microscope, membrane potential (MMP), calcium ion (Ca2+) and apoptosis rate were measured by flow cytometry, and the expressions of mitochondrial functional protein, mitochondrial dynein, mitochondrial autophagy protein as well as apoptosis related protein were detected by Western blot. The results showed that cell survival rate, SOD, CAT, GSH-Px, ATP and MMP gradually decreased with the increase of SiNPs concentration, while intracellular ROS, Ca2+, LDH and apoptosis rate increased with the increase of SiNPs concentration. In total cellular proteins,the expressions of mitochondrial functional proteins VDAC and UCP2 gradually increased, the expression of mitochondrial dynamic related protein DRP1 increased while the expressions of OPA1 and Mfn2 decreased. The expressions of mitophagy related proteins PINK1, Parkin and LC3Ⅱ/LC3Ⅰ increased and P62 gradually decreased, as well as the expressions of apoptosis related proteins Apaf-1, Cleaved-Caspase-3, Caspase-3, Caspase-9, Bax and Cyt-C. In mitochondrial proteins, the expressions of mitochondrial dynamic related proteins DRP1 and p-DRP1 were increased, while the expressions of OPA1 and Mfn2 were decreased. Expressions of mitochondrial autophagy associated proteins PINK1, Parkin, LC3II/LC3I increased, P62 decreased gradually, as well as the expressions of apoptosis related proteins Cleaved-Caspase-3, Caspase-3, and Caspase-9 increased, and Cyt-C expressions decreased. To further demonstrate the role of ROS and DRP1 in HT22 cell apoptosis induced by SiNPs, we selected the ROS inhibitor N-Acetylcysteine (NAC) and Dynamin-related protein 1 (DRP1) inhibitor Mdivi-1. The experimental results indicated that the above effects were remarkably improved after the use of inhibitors, further confirming that SiNPs induce the production of ROS in cells, activate DRP1, cause excessive mitochondrial division, induce mitophagy, destroy mitochondrial function and eventually lead to apoptosis.

Synergistic antimicrobial photodynamic therapy using gated mesoporous silica nanoparticles containing curcumin and polymyxin B.

Photodynamic Therapy is a therapy based on combining a non-toxic compound, known as photosensitizer (PS), and irradiation with light of the appropriate wavelength to excite the PS molecule. The photon absorption by the PS leads to reactive oxygen species generation and a subsequent oxidative burst that causes cell damage and death. In this work, we report an antimicrobial nanodevice that uses the activity of curcumin (Cur) as a PS for antimicrobial Photodynamic Therapy (aPDT), based on mesoporous silica nanoparticles in which the action of the classical antibiotic PMB is synergistically combined with the aPDT properties of curcumin to combat bacteria. The synergistic effect of the designed gated device in combination with irradiation with blue LED light (470 nm) is evaluated against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus epidermidis. The results show that the nanodevice exhibits a noteworthy antibacterial activity against these microorganisms, a much more significant effect than free Cur and PMB at equivalent concentrations. Thus, 0.1 µg/mL of MSNs-Cur-PMB eliminates a bacterial concentration of about 105 CFU/mL of E. coli, while 1 µg/mL of MSNs-Cur-PMB is required for P. aeruginosa and S. epidermidis. In addition, antibiofilm activity against the selected bacteria was also tested. We found that 0.1 mg/mL of MSNs-Cur-PMB inhibited 99 % biofilm formation for E. coli, and 1 mg/mL of MSNs-Cur-PMB achieved 90 % and 100 % inhibition of biofilm formation for S. epidermidis and P. aeruginosa, respectively.

Tannic acid- and N-acetylcysteine-chitosan-modified magnetic nanoparticles reduce hepatic oxidative stress in prediabetic rats.

Magnetic nanoparticles (MNPs) modified with tannic acid (TA) have shown remarkable success as an antioxidant and antimicrobial therapeutic agent. Herein, we report a synthetic procedure for the preparation of silica-coated MNPs modified with N-acetylcysteine-modified chitosan and TA. This was achieved by free-radical grafting of NAC onto chitosan (CS), a layer-by-layer technique for modifying negatively charged MNP@SiO2 nanoparticles with positively charged CS-NAC, and crosslinking CS with TA. The antioxidant and metabolic effects of MNP@SiO2-CS-NAC and MNP@SiO2-CS-NAC-TA nanoparticles were tested in a model of prediabetic rats with hepatic steatosis, the hereditary hypertriglyceridemic rats (HHTg). The particles exhibited significant antioxidant properties in the liver, increasing the activity of the antioxidant enzymes superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GPx), decreasing the concentration of the lipoperoxidation product malondialdehyde (MDA), and improving the antioxidant status determined as the ratio of reduced to oxidized glutathione; in particular, TA increased some antioxidant parameters. MNPs carrying antioxidants such as NAC and TA could thus represent a promising therapeutic agent for the treatment of various diseases accompanied by increased oxidative stress.

Porous Se@SiO2 nanospheres alleviate diabetic retinopathy by inhibiting excess lipid peroxidation and inflammation.

BACKGROUND: Lipid peroxidation is a characteristic metabolic manifestation of diabetic retinopathy (DR) that causes inflammation, eventually leading to severe retinal vascular abnormalities. Selenium (Se) can directly or indirectly scavenge intracellular free radicals. Due to the narrow distinction between Se's effective and toxic doses, porous Se@SiO2 nanospheres have been developed to control the release of Se. They exert strong antioxidant and anti-inflammatory effects. METHODS: The effect of anti-lipid peroxidation and anti-inflammatory effects of porous Se@SiO2 nanospheres on diabetic mice were assessed by detecting the level of Malondialdehyde (MDA), glutathione peroxidase 4 (GPX4), decreased reduced/oxidized glutathione (GSH/GSSG) ratio, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL) -1ß of the retina. To further examine the protective effect of porous Se@SiO2 nanospheres on the retinal vasculopathy of diabetic mice, retinal acellular capillary, the expression of tight junction proteins, and blood-retinal barrier destruction was observed. Finally, we validated the GPX4 as the target of porous Se@SiO2 nanospheres via decreased expression of GPX4 and detected the level of MDA, GSH/GSSG, TNF-α, IFN-γ, IL -1ß, wound healing assay, and tube formation in high glucose (HG) cultured Human retinal microvascular endothelial cells (HRMECs). RESULTS: The porous Se@SiO2 nanospheres reduced the level of MDA, TNF-α, IFN-γ, and IL -1ß, while increasing the level of GPX4 and GSH/GSSG in diabetic mice. Therefore, porous Se@SiO2 nanospheres reduced the number of retinal acellular capillaries, depletion of tight junction proteins, and vascular leakage in diabetic mice. Further, we identified GPX4 as the target of porous Se@SiO2 nanospheres as GPX4 inhibition reduced the repression effect of anti-lipid peroxidation, anti-inflammatory, and protective effects of endothelial cell dysfunction of porous Se@SiO2 nanospheres in HG-cultured HRMECs. CONCLUSION: Porous Se@SiO2 nanospheres effectively attenuated retinal vasculopathy in diabetic mice via inhibiting excess lipid peroxidation and inflammation by target GPX4, suggesting their potential as therapeutic agents for DR.