3D printing/electrospinning of a bilayered composite patch with antibacterial and antiadhesive properties for repairing abdominal wall defects.

The application of patch methods for repairing abdominal wall wounds presents a variety of challenges, such as adhesion and limited mobility due to inadequate mechanical strength and nonabsorbable materials. Among these complications, postoperative visceral adhesion and wound infection are particularly serious. In this study, a bilayered composite patch with a gelatin methacryloyl (GelMA)/sodium alginate (SA)-vancomycin (Van)@polycaprolactone (PCL) (GelMA/SA-Van@PCL) antibacterial layer was prepared via coaxial 3D printing and a polycaprolactone (PCL)-silicon dioxide (SiO2) antiadhesive layer (PCL-SiO2) was prepared via electrospinning and electrostatic spray for hernia repair. The evaluation of the physicochemical properties revealed that the composite patch had outstanding tensile properties (16 N cm-1), excellent swelling (swelling rate of 243.81 ± 12.52%) and degradation (degradation rate of 53.14 ± 3.02%) properties. Furthermore, the composite patch containing the antibiotic Van exhibited good antibacterial and long-term drug release properties. Both in vivo and in vitro experiments indicated that the composite patch displayed outstanding biocompatibility and antiadhesive properties and could prevent postoperative infections. In summary, the bilayered composite patch can effectively prevent postoperative complications while promoting tissue growth and repair and holds significant application potential in hernia repair.

Silica Nanoparticles Decorated with Ceria Quantum Dots Modulate Intra- and Extracellular Reactive Oxygen Species Formation and Selectively Reduce Human A375 Melanoma Cell Proliferation.

Nanomaterials show great promise for cancer treatment. Nonetheless, most nanomaterials lack selectivity for cancer cells, damaging healthy ones. Cerium dioxide (ceria, CeO2) nanoparticles have been shown to exert selective toxicity toward cancer cells due to the redox modulating properties they display as their size decreases. However, these particles suffer from poor suspension stability. The efficacy of CeO2 nanoparticles for cancer treatment is hampered by their innate high surface energy, which leads to particle agglomeration and, consequently, reactivity loss. This effect increases as particle size decreases; as such, quantum dots (QDs) suffer most from this phenomenon. In this study, it is proposed that silicon dioxide (silica, SiO2) nanoparticles can provide an inert platform for surface encrusted CeO2 QDs and that the resulting nanocomposite (hereafter QDCeO2/SiO2) not only will exhibit negligible agglomeration compared with CeO2 alone but also will improve the modulation of reactive oxygen species (ROS) leading to selective reduction of human A375 melanoma cell proliferation. The SiO2 nanoparticles had a bimodal size distribution with median particle size of 66 and 168 nm, while the CeO2 quantum dots encrusted on their surface had a size of 3.2 nm. An elevated Ce3+/Ce4+ ratio led to the QDCeO2/SiO2 nanocomposite displaying synergistic superoxide dismutase- and catalase-like activity, favoring the accumulation of ROS at pH 6.5 which translated into QDCeO2/SiO2 exerting selective oxidative stress in, and toward, the melanoma cells. Treatment with 50 µg mL-1 QDCeO2/SiO2 significantly reduced cell proliferation by 27% compared to untreated control cells in the colony formation assay. Treatment with either SiO2 or CeO2 alone did not affect the cell proliferation. These results highlight the benefit of dispersing CeO2 QDs on the surface of core nanoparticles and the resulting enhancement of selective redox reactivity and proliferation arrest when compared to CeO2 nanoparticles alone. Furthermore, the method employed here to encrust CeO2 QDs could lead to the facile synthesis of new nanocomposites with enhanced control of ROS activity, not only for in vitro studies using other cancer cell lines of interest but also in animal models and perhaps leading to clinical trials in melanoma patients.

Development of mesoporous magnetic nanoparticles supported idarubicin and investigation of apoptotic and cytotoxic effects on cancer cell lines.

BACKGROUND: Many methods are used for cancer treatment, especially chemotherapy. In addition to the their therapeutic effects, chemotherapeutic drugs also have serious disadvantages, such as not being cell and tissue-specific, causing toxicity in many tissues, and developing drug resistance. Many methods, especially nanocarriers, have been designed to overcome these disadvantages. METHODS AND RESULTS: In this study, we synthesized mesoporous silica iron oxide nanoparticles with different pore diameters and loaded idarubicin (6MFe3O4-NH2-IDA and 35MFe3O4-NH2-IDA). The synthesized molecules were characterized using FT-IR, XRD, and SEM methods. The cytotoxic effects of unbound idarubicin and idarubicin-loaded nanoparticles on MCF7 and HL-60 cell lines were examined by MTT test. Additionally, the expression of anti-apoptotic (Survivin and BCL-2) and apoptotic (BAX, PUMA, and NOXA) genes of the nanoparticles were measured by PCR method. As a result of the analyses, it was seen that nanoparticles with the desired properties and sizes were synthesized. In MTT analysis, it was observed that both nanoparticles dramatically decreased the IC50 value in cell lines. However, the 35MFe3O4-NH2-IDA molecule was found to have lower IC50 values. IC50 values ​​for pristine IDA, 6MFe3O4-NH2, and 35MFe3O4-NH2 at 24 h were found to be 3.56, 1.24 and 0.25 µM in the MCF7 cell line and 4.15, 1.16 and 0.34 µM in the HL-60 cell line, respectively. Additionally, apoptotic gene expression increased, and anti-apoptotic gene expression decreased. CONCLUSIONS: Our study demonstrates that the effectiveness of idarubicin can be significantly enhanced by its application with mesoporous nanocarriers. This enhancement is attributed to the controlled release of idarubicin from the nanocarrier, which circumvents drug resistance mechanisms, improves drug solubility, and increases the drug-carrying capacity per unit volume due to the porous structure of the carrier. These findings underscore the potential of the synthesized nanocarrier in cancer treatment and provide a clear direction for future research in this field.

Design of Scaffolds Based on Zinc-Modified Marine Collagen and Bilberry Leaves Extract-Loaded Silica Nanoparticles as Wound Dressings.

Purpose: In this study, wound dressings were designed using zinc-modified marine collagen porous scaffold as host for wild bilberry (WB) leaves extract immobilized in functionalized mesoporous silica nanoparticles (MSN). These new composites were developed as an alternative to conventional wound dressings. In addition to the antibacterial activity of classic antibiotics, a polyphenolic extract could act as an antioxidant and/or an anti-inflammatory agent as well. Methods: Wild bilberry leaves extract was prepared by ultrasound-assisted extraction in ethanol and its properties were evaluated by UV-Vis spectroscopy (radical scavenging activity, total amount of polyphenols, flavonoids, anthocyanins, and condensed tannins). The extract components were identified by HPLC, and the antidiabetic properties of the extract were evaluated via α-glucosidase inhibitory activity. Spherical MSN were modified with propionic acid or proline moieties by post-synthesis method and used as carriers for the WB leaves extract. The textural and structural features of functionalized MSN were assessed by nitrogen adsorption/desorption isotherms, small-angle XRD, SEM, TEM, and FTIR spectroscopy. The composite porous scaffolds were prepared by freeze drying of the zinc-modified collagen suspension containing WB extract loaded silica nanoparticles. Results: The properties of the new composites demonstrated enhanced properties in terms of thermal stability of the zinc-collagen scaffold, without altering the protein conformation, and stimulation of NCTC fibroblasts mobility. The results of the scratch assay showed contributions of both zinc ions from collagen and the polyphenolic extract incorporated in functionalized silica in the wound healing process. The extract encapsulated in functionalized MSN proved enhanced biological activities compared to the extract alone: better inhibition of P. aeruginosa and S. aureus strains, higher biocompatibility on HaCaT keratinocytes, and anti-inflammatory potential demonstrated by reduced IL-1ß and TNF-α levels. Conclusion: The experimental data shows that the novel composites can be used for the development of effective wound dressings.

A structured biomimetic nanoparticle as inflammatory factor sponge and autophagy-regulatory agent against intervertebral disc degeneration and discogenic pain.

Lower back pain (LBP) is a common condition closely associated with intervertebral disc degeneration (IDD), causing a significant socioeconomic burden. Inflammatory activation in degenerated discs involves pro-inflammatory cytokines, dysregulated regulatory cytokines, and increased levels of nerve growth factor (NGF), leading to further intervertebral disc destruction and pain sensitization. Macrophage polarization is closely related to autophagy. Based on these pathological features, a structured biomimetic nanoparticle coated with TrkA-overexpressing macrophage membranes (TMNP@SR) with a rapamycin-loaded mesoporous silica core is developed. TMNP@SR acted like sponges to adsorbe inflammatory cytokines and NGF and delivers the autophagy regulator rapamycin (RAPA) into macrophages through homologous targeting effects of the outer engineered cell membrane. By regulating autophagy activation, TMNP@SR promoted the M1-to-M2 switch of macrophages to avoid continuous activation of inflammation within the degenerated disc, which prevented the apoptosis of nucleus pulposus cells. In addition, TMNP@SR relieved mechanical and thermal hyperalgesia, reduced calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat IDD model. In summary, TMNP@SR spontaneously inhibits the aggravation of disc inflammation to alleviate disc degeneration and reduce the ingress of sensory nerves, presenting a promising treatment strategy for LBP induced by disc degeneration.

Sustainable Release Selenium Laden with SiO2 Restoring Peripheral Nerve Injury via Modulating PI3K/AKT Pathway Signaling Pathway.

Background: Inhibiting ROS overproduction is considered a very effective strategy for the treatment of peripheral nerve injuries, and Se has a remarkable antioxidant effect; however, since the difference between the effective concentration of Se and the toxic dose is not large, we synthesized a nanomaterial that can release Se slowly so that it can be used more effectively. Methods: Se@SiO2 NPs were synthesized using a mixture of Cu2-x Se nanocrystals, and the mechanism of action of Se@SiO2 NPs was initially explored by performing sequencing, immunofluorescence staining and Western blotting of cellular experiments. The mechanism of action of Se@SiO2 NPs was further determined by performing behavioral assays after animal experiments and by sampling the material for histological staining, immunofluorescence staining, and ELISA. The effects, mechanisms and biocompatibility of Se@SiO2 NPs for peripheral nerve regeneration were determined. Results: Porous Se@SiO2 was successfully synthesized, had good particle properties, and could release Se slowly. CCK-8 experiments revealed that the optimal experimental doses were 100 µM H2O2 and 200 µg/mL Se@SiO2, and RNA-seq revealed that porous Se@SiO2 was associated with cell proliferation, apoptosis, and the PI3K/AKT pathway. WB showed that porous Se@SiO2 could increase the expression of cell proliferation antigens (PCNA and S100) and antiapoptotic proteins (Bcl-2), decrease the expression of proapoptotic proteins (Bax), and increase the expression of antioxidative stress proteins (Nrf2, HO-1, and SOD2). EdU cell proliferation and ROS fluorescence assays showed that porous Se@SiO2 promoted cell proliferation and reduced ROS levels. The therapeutic effect of LY294002 (a PI3K/AKT pathway inhibitor) was decreased significantly and its effect was lost when it was added simultaneously with porous Se@SiO2. Animal experiments revealed that the regenerated nerve fiber density, myelin thickness, axon area, gastrocnemius muscle wet-to-weight ratio, myofiber area, sciatic nerve function index (SFI), CMAP, apoptotic cell ratio, and levels of antioxidative stress proteins and anti-inflammatory factors were increased following the administration of porous Se@SiO2. The levels of oxidative stress proteins and anti-inflammatory factors were significantly greater in the Se@SiO2 group than in the PNI group, and the effect of LY294002 was decreased significantly and was lost when it was added simultaneously with porous Se@SiO2. Conclusion: Se@SiO2 NPs are promising, economical and effective Se-releasing nanomaterials that can effectively reduce ROS production, inhibit apoptosis and promote cell proliferation after nerve injury via the PI3K/AKT pathway, ultimately accelerating nerve regeneration. These findings could be used to design new, promising drugs for the treatment of peripheral nerve injury.

Biofilm microenvironment-activated multimodal therapy nanoplatform for effective anti-bacterial treatment and wound healing.

Antimicrobial drug development faces challenges from bacterial resistance, biofilms, and excessive inflammation. Here, we design an intelligent nanoplatform utilizing mesoporous silica nanoparticles doped with copper ions for loading copper sulfide (DM/Cu2+-CuS). The mesoporous silica doped with tetrasulfide bonds responds to the biofilm microenvironment (BME), releasing Cu2+ions, CuS along with hydrogen sulfide (H2S) gas. The release of hydrogen sulfide within 72 h reached 793.5 µM, significantly higher than that observed with conventional small molecule donors. H2S induces macrophages polarization towards the M2 phenotype, reducing inflammation and synergistically accelerating endothelial cell proliferation and migration with Cu2+ions. In addition, H2S disrupts extracellular DNA within biofilms, synergistically photothermal enhanced peroxidase-like activity of CuS to effectively eradicate biofilms. Remarkably, DM-mediated consumption of endogenous glutathione enhances the anti-biofilm activity of H2S and improves oxygen species (ROS) destruction efficiency. The combination of photothermal therapy (PTT), chemodynamic therapy (CDT), and gas treatment achieves sterilization rates of 99.3 % and 99.6 % against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), respectively, in vitro under 808 nm laser irradiation. Additionally, in vivo experiments demonstrate a significant biosafety and antibacterial potential. In summary, the H2S donor developed in this study exhibits enhanced biocompatibility and controlled release properties. By integrating BME-responsive gas therapy with antibacterial ions, PTT and CDT, a synergistic multimodal strategy is proposed to offer new therapeutic approaches for wound healing. STATEMENT OF SIGNIFICANCE: The advanced DMOS/Cu2+-CuS (DMCC) multimodal therapeutic nanoplatform has been developed for the treatment of drug-resistant bacterial wound infections and has exhibited enhanced therapeutic efficacy through the synergistic effects of photothermal therapy, chemodynamic therapy, Cu2+ions, and H2S. The DMCC exhibited exceptional biocompatibility and could release CuS, Cu2+, and H2S in response to elevated concentrations of glutathione within the biofilm microenvironment. H2S effectively disrupted the biofilm structure. Meanwhile, peroxidase activity of CuS combined with GSH-mediated reduction of Cu2+ to Cu+ generated abundant hydroxyl radicals under acidic conditions, leading to efficient eradication of pathogenic bacteria. Furthermore, both H2S and Cu2+ could modulate M2 macrophages polarization and regulate immune microenvironment dynamics. These strategies collectively provided a novel approach for developing antibacterial nanomedical platforms.

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.

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.

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.

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.

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.

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.

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.

In situ generation of copper(â ¡)/diethyldithiocarbamate complex through tannic acid/copper(â ¡) network coated hollow mesoporous silica for enhanced cancer chemodynamic therapy.

The Cu2+ complex formed by the coordination of disulfiram (DSF) metabolite diethyldithiocarbamate (DTC), Cu(DTC)2, can effectively inhibit tumor growth. However, insufficient Cu2+ levels in the tumor microenvironment can impact tumor-suppressive effects of DTC. In this study, we proposed a Cu2+ and DSF tumor microenvironment-targeted delivery system. This system utilizes hollow mesoporous silica (HMSN) as a carrier, after loading with DSF, encases it using a complex of tannic acid (TA) and Cu2+ on the outer layer. In the slightly acidic tumor microenvironment, TA/Cu undergoes hydrolysis, releasing Cu2+ and DSF, which further form Cu(DTC)2 to inhibit tumor growth. Additionally, Cu2+ can engage in a Fenton-like reaction with H2O2 in the tumor microenvironment to form OH, therefore, chemodynamic therapy (CDT) and Cu(DTC)2 are used in combination for tumor therapy. In vivo tumor treatment results demonstrated that AHD@TA/Cu could accumulate at the tumor site, achieving a tumor inhibition rate of up to 77.6 %. This study offers a novel approach, circumventing the use of traditional chemotherapy drugs, and provides valuable insights into the development of in situ tumor drug therapies.

Design of an anticancer organoruthenium complex as the guest and polydiacetylene-coated fluorogenic nanocarrier as the host: engineering nanocarrier using ene-yne conjugation for sustained guest release, enhanced anticancer activity and reduced in vivo toxicity.

Despite the enormous efforts made over the past two decades to develop metallodrugs and nanocarriers for metallodrug delivery, there are still few precise strategies that aim to optimize the design of both metallodrugs and metallodrug carriers jointly in a concerted effort. In this work, three half-sandwich ruthenium(II) complexes with pyridylimidazo[1,5-a]pyridine ligand functionalized with polycyclic aromatic moiety (Ru(nap), Ru(ant), Ru(pyr)) are evaluated as possible anticancer candidates and polydiacetylene (PDA)-coated amino-functionalized mesoporous silica nanoparticles (AMSNs) are designed as a functional nanocarrier for drug delivery. Ru(pyr) exhibits higher cytotoxicity in HT-29 colorectal cancer cells compared to other complexes and cis-platin, but it does not exhibit better cellular uptake. Ru(pyr) is found to be preferentially accumulated in plasma, mitochondria, and ER-Golgi membrane. The complex induces cell cycle arrest in the G0/G1 phase, while higher concentrations cause programmed cell death via apoptosis. Ru(pyr) influences cancer cell adhesion property and acts as an antioxidant in HT-29 cells. In order to modulate the anticancer potency of Ru(pyr), AMSNs are used to encapsulate the complex, and then diacetylene self-assembly is allowed to deposit on the surface of the nanoparticles. Subsequently, the nanoparticles undergo topopolymerization, which results in π-conjugated PDA-Ru(pyr)@AMSNs. Owing to the ene-yne polymeric skeleton in the backbone, the non-fluorescent AMSNs turn into red-emissive particles, which are exploited for cell imaging applications. The release profile analysis reveals that such a π-conjugated polymer prevents the premature release of the complex from porous silica nanoparticles with the accelerated release of the complex in an acidic medium compared to physiological conditions. The PDA gatekeepers have also been proven to enhance the cellular internalization of Ru(pyr) with slow continuous release from the nanoformulation. Zebrafish embryo toxicity analysis suggests that the PDA-coated nanocarriers could be suitable candidates for in vivo investigations.

Extracellular and intracellular effects of bioactive glass nanoparticles on osteogenic differentiation of bone marrow mesenchymal stem cells and bone regeneration in zebrafish osteoporosis model.

Bioactive glass nanoparticles (BGNs) are well-recognized multifunctional biomaterials for bone tissue regeneration due to their capability to stimulate various cellular processes through released biologically active ions. Understanding the correlation between BGN composition and cellular responses is key to developing clinically usable BGN-based medical devices. This study investigated the influence of CaO content of binary SiO2-CaO BGNs (CaO ranging from 0 to 10 mol%) on osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and in vivo bone regeneration in zebrafish osteoporosis model. The results showed that BGNs could promote osteogenic differentiation of rBMSCs by indirectly releasing active ions or directly interacting with rBMSCs by internalization. In both situations, BGNs of a higher CaO content could promote the osteogenic differentiation of rBMSCs to a greater extent. The internalized BGNs could activate the transcription factors RUNX2 and OSX, leading to the expression of osteogenesis-related genes. The results in the zebrafish osteoporosis model indicated that the presence of BGNs of higher CaO contents could enhance bone regeneration and rescue dexamethasone-induced osteoporosis to a greater extent. These findings demonstrate that BGNs can stimulate osteogenic differentiation of rBMSCs by releasing active ions or internalization. A higher CaO content facilitates osteogenesis and bone regeneration of zebrafish as well as relieving dexamethasone-induced osteoporosis. The zebrafish osteoporosis model can be a potent tool for evaluating the in vivo bone regeneration effects of bioactive materials. STATEMENT OF SIGNIFICANCE: Bioactive glass nanoparticles (BGNs) are increasingly used as fillers of nanocomposites or as delivery platforms of active ions to regenerate bone tissue. Various studies have shown that BGNs can enhance osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by releasing active ions. However, the correlation between BGN composition and cellular responses and in vivo bone regeneration effect has still not been well investigated. Establishment of a suitable in vivo animal model for investigating this correlation is also challenging. The present study reports the influence of CaO content in binary SiO2-CaO BGNs on osteogenic differentiation of BMSCs extracellularly and intracellularly. This study also demonstrates the suitability of zebrafish osteoporosis model to investigate in vivo bone regeneration effect of BGNs.

3D Printed SiO2-Tricalcium Phosphate Scaffolds Loaded with Carvacrol Nanoparticles for Bone Tissue Engineering Application.

Bone damage resulting from trauma or aging poses challenges in clinical settings that need to be addressed using bone tissue engineering (BTE). Carvacrol (CA) possesses anti-inflammatory, anticancer, and antibacterial properties. Limited solubility and physicochemical stability restrict its biological activity, requiring a stable carrier system for delivery. Here, we investigate the utilization of a three-dimensional printed (3DP) SiO2-doped tricalcium phosphate (TCP) scaffold functionalized with carvacrol-loaded lipid nanoparticles (CA-LNPs) to improve bone health. It exhibits a negative surface charge with an entrapment efficiency of ∼97% and size ∼129 nm with polydispersity index (PDI) and zeta potential values of 0.18 and -16 mV, respectively. CA-LNPs exhibit higher and long-term release over 35 days. The CA-LNP loaded SiO2-doped TCP scaffold demonstrates improved antibacterial properties against Staphylococcus aureus and Pseudomonas aeruginosa by >90% reduction in bacterial growth. Functionalized scaffolds result in 3-fold decrease and 2-fold increase in osteosarcoma and osteoblast cell viability, respectively. These findings highlight the therapeutic potential of the CA-LNP loaded SiO2-doped TCP scaffold for bone defect treatment.

Silica Nanoparticle Size Determines the Mechanisms Underlying the Inhibition of Iron Oxide Nanoparticle Uptake by Daphnia magna.

Aquatic environments are complicated systems that contain different types of nanoparticles (NPs). Nevertheless, recent studies of NP toxicity, and especially those that have focused on bioaccumulation have mostly investigated only a single type of NPs. Assessments of the environmental risks of NPs that do not consider co-exposure regimes may lead to inaccurate conclusions and ineffective environmental regulation. Thus, the present study examined the effects of differently sized silica NPs (SiO2 NPs) on the uptake of iron oxide NPs (Fe2O3 NPs) by the zooplankton Daphnia magna. Both SiO2 NPs and Fe2O3 NPs were well dispersed in the experimental medium without significant heteroaggregation. Although all three sizes of SiO2 NPs inhibited the uptake of Fe2O3 NPs, the underlying mechanisms differed. SiO2 NPs smaller than the average mesh size (∼200 nm) of the filtering apparatus of D. magna reduced the accumulation of Fe2O3 NPs through uptake competition, whereas larger SiO2 NPs inhibited the uptake of Fe2O3 NPs mainly by reducing the water filtration rate of the daphnids. Overall, in evaluations of the risks of NPs in the natural environment, the different mechanisms underlying the effects of NPs of different sizes on the uptake of dissimilar NPs should be considered.