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.

Apolar Extracts of St. John's Wort Alleviate the Effects of ß-Amyloid Toxicity in Early Alzheimer's Disease.

Hypericum perforatum (St. John's wort) has been described to be beneficial for the treatment of Alzheimer's disease (AD). Different extractions have demonstrated efficiency in mice and humans, esp. extracts with a low hypericin and hyperforin content to reduce side effects such as phototoxicity. In order to systematically elucidate the therapeutic effects of H. perforatum extracts with different polarities, APP-transgenic mice were treated with a total ethanol extract (TE), a polar extract obtained from TE, and an apolar supercritical CO2 (scCO2) extract. The scCO2 extract was formulated with silicon dioxide (SiO2) for better oral application. APP-transgenic mice were treated with several extracts (total, polar, apolar) at different concentrations. We established an early treatment paradigm from the age of 40 days until the age of 80 days, starting before the onset of cerebral ß-amyloid (Aß) deposition at 45 days of age. Their effects on intracerebral soluble and insoluble Aß were analyzed using biochemical analyses. Our study confirms that the scCO2H. perforatum formulation shows better biological activity against Aß-related pathological effects than the TE or polar extracts. Clinically, the treatment resulted in a dose-dependent improvement in food intake with augmentation of the body weight, and, biochemically, it resulted in a significant reduction in both soluble and insoluble Aß (-27% and -25%, respectively). We therefore recommend apolar H. perforatum extracts for the early oral treatment of patients with mild cognitive impairment or early AD.

Co-Delivery of Gemcitabine and Honokiol by Lipid Bilayer-Coated Mesoporous Silica Nanoparticles Enhances Pancreatic Cancer Therapy via Targeting Depletion of Tumor Stroma.

Syndecan-1 (SDC1) modified lipid bilayer (LB)-coated mesoporous silica nanoparticles (MSN) to co-deliver gemcitabine (GEM) and honokiol (HNK) were prepared for the targeting treatment of pancreatic cancer. The encapsulation efficiencies of GEM and HNK in SDC1-LB-MSN-GEM/HNK were determined to be 60.3 ± 3.2% and 73.0 ± 1.1%. The targeting efficiency of SDC1-LB-MSN-GEM/HNK was investigated in BxPC-3 cells in vitro. The fluorescence intensity in the cells treated with SDC1-LB-MSN-Cou6 was 2-fold of LB-MSN-Cou6-treated cells, which was caused by SDC1/IGF1R-mediated endocytosis. As anticipated, its cytotoxicity was significantly increased. Furthermore, the mechanism was verified that SDC1-LB-MSN-HNK induced tumor cell apoptosis through the mitochondrial apoptosis pathway. Finally, the biodistribution, tumor growth inhibition, and preliminary safety studies were performed on BALB/c nude mice bearing BxPC-3 tumor models. The tumor growth inhibition index of SDC1-LB-MSN-GEM/HNK was 56.19%, which was 1.45-fold and 1.33-fold higher than that of the free GEM/HNK and LB-MSN-GEM/HNK treatment groups, respectively. As a result, SDC1-LB-MSN-GEM/HNK combined advantages of both GEM and HNK and simultaneously targeted and eliminated pancreatic cancerous and cancer-associated stromal cells. In summary, the present study demonstrated a new strategy of synergistic GEM and HNK to enhance the therapeutic effect of pancreatic cancer via the targeting depletion of tumor stroma.

From Basic Research to Clinical Practice: Considerations for Treatment Drugs for Silicosis.

Silicosis, characterized by irreversible pulmonary fibrosis, remains a major global public health problem. Nowadays, cumulative studies are focusing on elucidating the pathogenesis of silicosis in order to identify preventive or therapeutic antifibrotic agents. However, the existing research on the mechanism of silica-dust-induced pulmonary fibrosis is only the tip of the iceberg and lags far behind clinical needs. Idiopathic pulmonary fibrosis (IPF), as a pulmonary fibrosis disease, also has the same problem. In this study, we examined the relationship between silicosis and IPF from the perspective of their pathogenesis and fibrotic characteristics, further discussing current drug research and limitations of clinical application in silicosis. Overall, this review provided novel insights for clinical treatment of silicosis with the hope of bridging the gap between research and practice in silicosis.

The Effect of Silica Nanoparticles (SiNPs) on Cytotoxicity, Induction of Oxidative Stress and Apoptosis in Breast Cancer Cell Lines.

Breast cancer is one of the most common cancers in women. Silica nanoparticles (SiNPs) belong to the group of often-used nanoparticles in biomedical applications. The mechanisms of the cytotoxicity, apoptosis, and oxidative stress induced by the 5-15 nm SiNPs still remain unclear. The aim of the study was to evaluate the anti-cancer effect and mechanism of action of SiNPs in breast cancer cell lines. The breast cancer MDA-MB-231 and ZR-75-1 cell lines were analyzed using MTT assay, flow cytometry, and spectrophotometric methods. In this paper, we presented findings about the cytotoxicity, apoptosis, and oxidative stress in both breast cancer cell lines. We indicated that 5-15 nm SiNPs induced dose-dependent cytotoxicity in MDA-MB-231 and ZR-75-1 cells. Moreover, we demonstrated that the process of apoptosis in the studied cell lines was associated with a decrease in the mitochondrial membrane potential (ΔΨm) and an increase in the activity of caspase-9 and caspase-3. Based on the obtained results, 5-15 nm SiNPs are able to induce the mitochondrial apoptosis pathway. Analyzed nanoparticles have also been found to cause an increase in selected oxidative stress parameters in both breast cancer cell lines. The presented study provides an explanation of the possible mechanisms of 5-15 nm SiNPs action in breast cancer cells.

Comparative evaluation of retention and cariostatic effect of glass ionomer, hydrophobic & hydrophilic resin-based sealants: a systematic review and meta-analysis.

OBJECTIVE: To compare the effectiveness of hydrophilic resin-based versus hydrophobic resin-based and glass-ionomer pit and fissure sealants. METHODS: The review was registered with Joanna Briggs Institute and followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed, Google Scholar, Virtual Health Library, and Cochrane Central Register of Controlled Trials were searched from 2009-2019 using appropriate keywords. We included randomized controlled trials and randomized split-mouth trials conducted among 6-13-year-old children. The quality of included trials was assessed using modified Jadad criteria and risk of bias using guidelines specified by Cochrane. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) guidelines were used to assess the overall quality of studies. We used the random-effects model for meta-analysis. Relative risk (RR) and confidence intervals (CI) were calculated & heterogeneity was tested using I² statistic. RESULTS: Six randomized clinical trials and five split-mouth trials met the inclusion criteria. The outlier augmenting the heterogeneity was omitted. Based on very-low to low-quality evidence, loss of hydrophilic resin-based sealants was less likely as compared to glass-ionomer fissure sealants (4 trials at 6 months; RR = 0.59; CI = 0.40-0.86), while it was similar or slightly lower than hydrophobic resin-based sealants (6 trials at 6 months; RR = 0.96; CI = 0.89-1.03); (6 trials at 12 months; RR = 0.79; CI = 0.70-0.89); (2 trials at 18 months; RR = 0.77; CI = 0.48-0.25). CONCLUSION: This study revealed that retention of hydrophilic resin-based sealants is better than glass ionomer sealants but similar to hydrophobic resin-based sealants. However, higher-quality evidence is necessary to underpin the outcomes.

Protective effects of intranasal curcumin on silica-induced lung damage.

OBJECTIVE: Being anti-inflammatory and an antioxidant in nature, curcumin has been studied for its anti-asthmatic effects, but its impact on silicosis has not been investigated before. It is a form of occupational lung illness caused by inhaling crystalline silica. It is particularly common among those who work in construction-related sectors. Therefore, present study has been undertaken to investigate impact of intranasal curcumin on silica induced lung damage in mice model of silicosis. MATERIALS AND METHODS: Mice model of silicosis was developed by intranasal silica instillation (2.5 mg/mice) for different durations mainly 7, 14 and 21 days, where the longest duration of silica exposure (21 days) mimics chronic occupational exposure of silica dust leading to silicosis. Curcumin (5 mg/kg,i.n) and /or dexamethasone, a known corticosteroid (10 mg/kg,i.p) was administered an hour prior to silica administration. RESULTS: Present study revealed silica induced lung damage in the mice model of silicosis characterized by airway inflammation, collagen deposition and enhanced expression of fibrosis markers (MMP-9, α-SMA, Hydroxyproline), which were significantly reduced in curcumin treatment groups. Inhibitory effects of curcumin were compared with standard drug, dexamethasone, a corticosteroid and was found better in protecting structural alterations in the lung. Damaged and abnormal mitochondria (enlarged and irregular shapes) were observed in silicosis group which were reduced in curcumin and dexamethasone treatment groups as revealed in transmission electron microscopic studies. CONCLUSIONS: Present study shows protective effects of intranasal curcumin on silica-induced airway inflammation and structural changes thereby lung damage. Hence, it can be considered as an alternative and complementary medication for silicosis.

Cartilage targeting therapy with reactive oxygen species-responsive nanocarrier for osteoarthritis.

Targeting cartilage is a promising strategy for the treatment of osteoarthritis, and various delivery vehicles were developed to assist the therapeutic agents into cartilage. However, the underlying biomechanisms and potential bioactivities remain oversimplified. Inspired by oxidative stress in the pathogenesis of osteoarthritis, we firstly testified the antioxidant capacity of a synthetic small molecule compound, oltipraz (OL), to the chondrocytes treated by IL-1ß. Then a functional reactive oxygen species (ROS) responsive nanocarrier, mesoporous silica nanoparticles (MSN) modified with methoxy polyethylene glycol-thioketal, was constructed. In vitro biomolecular results showed that compared with OL alone, MSN-OL could significantly activate Nrf2/HO-1 signaling pathway, which exhibited better ROS-scavenging proficiency and greater anti-apoptotic ability to protect mitochondrial membrane potential of chondrocytes. Further bioinformatics analysis revealed that MSN-OL suppressed clusters of genes associated with extracellular matrix organization, cell apoptosis and cellular response to oxidative stress. Animal experiments further confirmed the great cartilage-protecting ability of MSN-OL through upregulating the expression of Nrf2/HO-1 signaling pathway without obvious toxicity. In summary, this study provided a delivery system through ROS-responsive regulation of the therapeutic agents into chondrocytes of the cartilage, and confirmed the exact biological mechanisms of this innovative strategy.

Platelet-Membrane-Coated Nanoparticles Enable Vascular Disrupting Agent Combining Anti-Angiogenic Drug for Improved Tumor Vessel Impairment.

Compared with traditional chemotherapeutics, vascular disruption agents (VDAs) have the advantages of rapidly blocking the supply of nutrients and starving tumors to death. Although the VDAs are effective under certain scenarios, this treatment triggers angiogenesis in the later stage of therapy that frequently leads to tumor recurrence and treatment failure. Additionally, the nonspecific tumor targeting and considerable side effects also impede the clinical applications of VDAs. Here we develop a customized strategy that combines a VDA with an anti-angiogenic drug (AAD) using mesoporous silica nanoparticles (MSNs) coated with platelet membrane for the self-assembled tumor targeting accumulation. The tailor-made nanoparticles accumulate in tumor tissues through the targeted adhesion of platelet membrane surface to damaged vessel sites, resulting in significant vascular disruption and efficient anti-angiogenesis in animal models. This study demonstrates the promising potential of combining VDA and AAD in a single nanoplatform for tumor eradication.

Lycopene, Mesoporous Silica Nanoparticles and Their Association: A Possible Alternative against Vulvovaginal Candidiasis?

Commonly found colonizing the human microbiota, Candida albicans is a microorganism known for its ability to cause infections, mainly in the vulvovaginal region known as vulvovaginal candidiasis (VVC). This pathology is, in fact, one of the main C. albicans clinical manifestations, changing from a colonizer to a pathogen. The increase in VVC cases and limited antifungal therapy make C. albicans an increasingly frequent risk in women's lives, especially in immunocompromised patients, pregnant women and the elderly. Therefore, it is necessary to develop new therapeutic options, especially those involving natural products associated with nanotechnology, such as lycopene and mesoporous silica nanoparticles. From this perspective, this study sought to assess whether lycopene, mesoporous silica nanoparticles and their combination would be an attractive product for the treatment of this serious disease through microbiological in vitro tests and acute toxicity tests in an alternative in vivo model of Galleria mellonella. Although they did not show desirable antifungal activity for VVC therapy, the present study strongly encourages the use of mesoporous silica nanoparticles impregnated with lycopene for the treatment of other human pathologies, since the products evaluated here did not show toxicity in the in vivo test performed, being therefore, a topic to be further explored.

Mesoporous silica nanoparticles combined with AKR1C3 siRNA inhibited the growth of castration-resistant prostate cancer by suppressing androgen synthesis in vitro and in vivo.

Intracrine androgen synthesis plays a critical role in the development of castration-resistant prostate cancer (CRPC). Aldo-keto reductase family 1 member C3 (AKR1C3) is a vital enzyme in the intracrine androgen synthesis pathway. In this study, mesoporous silica nanoparticles (MSNs) were employed to deliver small interfering RNA targeting AKR1C3 (siAKR1C3) to downregulate AKR1C3 expression in CPRC cells. The optimal weight ratio of MSNs/siAKR1C3 was determined by a gel retardation assay. Prostate cancer cells such as VCaP cells, which intracrinally express AKR1C3, and LNCaP-AKR1C3 cells stably transfected with AKR1C3 were used to investigate the antitumour effect of MSNs-siAKR1C3. Fluorescence detection and Western blot analyses were applied to confirm the entrance of MSNs-siAKR1C3 into the cells. A SRB (Sulforhodamine B) assay was employed to assess the cell viability, and a radioimmunoassay was used to measure the androgen concentration. Moreover, real-time PCR (RT-PCR), Western blot analysis and ELISA were used to determine the transcription and expression of prostate-specific antigen (PSA), AKR1C3 and androgen receptor (AR). Meanwhile, a reporter gene assay was performed to determine the AR activity. Additionally, a castrated nude mouse xenograft tumour model was produced to verify the inhibitory effect of MSNs-siAKR1C3 in vivo. The results showed that the optimal weight ratio of MSNs/siAKR1C3 was 140:1, and the complex could effectively enter cells, downregulate AKR1C3 expression, reduce the androgen concentration, inhibit AR activation, and inhibit CRPC development both in vitro and in vivo. These results indicate that decreasing intracrine androgen synthesis and inactivating AR signals by MSNs-siAKR1C3 may be a potential effective method for CRPC treatment.

Dental Applications of Carbon Nanotubes.

Glass ionomer cements and resin-based composites are promising materials in restorative dentistry. However, their limited mechanical properties and the risk of bulk/marginal fracture compromise their lifespan. Intensive research has been conducted to understand and develop new materials that can mimic the functional behavior of the oral cavity. Nanotechnological approaches have emerged to treat oral infections and become a part of scaffolds for tissue regeneration. Carbon nanotubes are promising materials to create multifunctional platforms for dental applications. This review provides a comprehensive survey of and information on the status of this state-of-the-art technology and describes the development of glass ionomers reinforced with carbon nanotubes possessing improved mechanical properties. The applications of carbon nanotubes in drug delivery and tissue engineering for healing infections and lesions of the oral cavity are also described. The review concludes with a summary of the current status and presents a vision of future applications of carbon nanotubes in the practice of dentistry.

Bimatoprost-Loaded Silica Shell-Coated Nanoparticles-Laden Soft Contact Lenses to Manage Glaucoma: In Vitro and In Vivo Studies.

Currently, glaucoma is managed by frequent instillation of bimatoprost eye drop therapy, which showed very poor ocular bioavailability. Contact lens is widely used as medical device to improve the drug retention on the ocular tissues. However, the traditional methods of drug loading in the contact lens matrix showed high burst release and changes the optophysical properties of the contact lens material. In this paper, a novel bimatoprost-loaded silica shell nanoparticles-laden soft contact lenses were developed to achieve sustain drug delivery without altering the optophysical properties of the contact lens. Silica-shell nanoparticles were prepared using octyltrimethoxysilane (OTMS) and microemulsion. Traditional soaking method (SM-BT), direct bimatoprost loading method (DL-BT), and microemulsion-laden contact lens (ME-BT) were developed for comparison. The silica shell-coated nanoparticles-laden soft contact lenses (SiS-BT) showed improved swelling, transmittance, oxygen permeability, and lysozyme adherence compared to SM-BT, DL-BT, and ME-BT lenses. The DL-BT and ME-BT batch showed high bimatoprost lost/leaching during extraction and sterilization steps, with low cumulative drug release. Also, SiS-BT lens showed sustain bimatoprost release for 96 h. In a rabbit tear fluid model, the SiS-BT lens showed high bimatoprost concentration for 72 h compared to ME-BT lens and eye drop therapy. Based on histopathological studies of cornea, the SiS-BT lens was found to be safe for human applications. The data demonstrated the novel application of silica shell nanoparticles to deliver bimatoprost from the contact lens for extended period of time without altering the optophysical properties of the contact lens.

Targeted Theranostic Nano Vehicle Endorsed with Self-Destruction and Immunostimulatory Features to Circumvent Drug Resistance and Wipe-Out Tumor Reinitiating Cancer Stem Cells.

The downsides of conventional cancer monotherapies are profound and enormously consequential, as drug-resistant cancer cells and cancer stem cells (CSC) are typically not eliminated. Here, a targeted theranostic nano vehicle (TTNV) is designed using manganese-doped mesoporous silica nanoparticle with an ideal surface area and pore volume for co-loading an optimized ratio of antineoplastic doxorubicin and a drug efflux inhibitor tariquidar. This strategically framed TTNV is chemically conjugated with folic acid and hyaluronic acid as a dual-targeting entity to promote folate receptor (FR) mediated cancer cells and CD44 mediated CSC uptake, respectively. Interestingly, surface-enhanced Raman spectroscopy is exploited to evaluate the molecular changes associated with therapeutic progression. Tumor microenvironment selective biodegradation and immunostimulatory potential of the MSN-Mn core are safeguarded with a chitosan coating which modulates the premature cargo release and accords biocompatibility. The superior antitumor response in FR-positive syngeneic and CSC-rich human xenograft murine models is associated with a tumor-targeted biodistribution, favorable pharmacokinetics, and an appealing bioelimination pattern of the TTNV with no palpable signs of toxicity. This dual drug-loaded nano vehicle offers a feasible approach for efficient cancer therapy by on demand cargo release in order to execute complete wipe-out of tumor reinitiating cancer stem cells.

Silica solutions (SL) is efficacy in the treatment of chronic periodontitis: a case control study.

AIM: The objective of this study was to compare the efficacy of supportive periodontal therapy (i.e. scaling and rooth planning, SRP) alone versus a chemical device silica dioxide (SiO2) colloidal solutions (SL) used in association with SRP in the treatment of chronic periodontitis in adult patients. MATERIALS AND METHODS: A total of 20 patients with a diagnosis of chronic periodontitis (40 localized chronic periodontitis sites) in the age group of 35 to 55 were selected. None of these patients have previously received any surgical or non-surgical periodontal therapy and demonstrated radiographic evidence of moderate bone loss. Two non-adjacent sites in separate quadrants were selected in each patient to monitorize treatment efficacy (split mouth design). Clinical pocket depth (PD) and microbial analysis (MA) were analyzed at baseline and 15th day. SPSS program and paired simple statistic T-test were used to detect significant differences. RESULTS: Total bacteria loading, Tannerella Forsitia and Treponema Denticola loading were statistically reduced when SiO2 is locally delivered. CONCLUSIONS: SL gel is an adiuvant therapy which should be added to SRP in the management of moderate to severe chronic periodontitis.

Silica dioxide colloidal solutions is efficient in the treatment of chronic periodontitis: a case control study.

The objective of this study was to compare the efficacy of supportive periodontal therapy (i.e. scaling and rooth planning, SRP) alone versus a chemical device silica dioxide (SiO2) colloidal solutions (SDCS) used in association with SRP in the treatment of chronic periodontitis in adult patients. A total of 20 patients with a diagnosis of chronic periodontitis (40 localized chronic periodontitis sites) in the age group of 35 to 55 were selected. None of these patients have previously received any surgical or non-surgical periodontal therapy and demonstrated radiographic evidence of moderate bone loss. Two non-adjacent sites in separate quadrants were selected in each patient to monitorize treatment efficacy (split mouth design). Clinical pocket depth (PD) and microbial analysis (MA) were analyzed at baseline and 15th day. SPSS program and paired simple statistic T-test were used to detect significant differences. Total bacteria loading, Tannerella Forsitia and Treponema Denticola loading were statistically reduced when SiO2 is locally delivered. SDCS gel is an adjuvant therapy which should be added to SRP in the management of moderate to severe chronic periodontitis.

Targeted Stimuli-Responsive Mesoporous Silica Nanoparticles for Bacterial Infection Treatment.

The rise of antibiotic resistance and the growing number of biofilm-related infections make bacterial infections a serious threat for global human health. Nanomedicine has entered into this scenario by bringing new alternatives to design and develop effective antimicrobial nanoweapons to fight against bacterial infection. Among them, mesoporous silica nanoparticles (MSNs) exhibit unique characteristics that make them ideal nanocarriers to load, protect and transport antimicrobial cargoes to the target bacteria and/or biofilm, and release them in response to certain stimuli. The combination of infection-targeting and stimuli-responsive drug delivery capabilities aims to increase the specificity and efficacy of antimicrobial treatment and prevent undesirable side effects, becoming a ground-breaking alternative to conventional antibiotic treatments. This review focuses on the scientific advances developed to date in MSNs for infection-targeted stimuli-responsive antimicrobials delivery. The targeting strategies for specific recognition of bacteria are detailed. Moreover, the possibility of incorporating anti-biofilm agents with MSNs aimed at promoting biofilm penetrability is overviewed. Finally, a comprehensive description of the different scientific approaches for the design and development of smart MSNs able to release the antimicrobial payloads at the infection site in response to internal or external stimuli is provided.

Periodic Mesoporous Organosilica Nanoparticles with BOC Group, towards HIFU Responsive Agents.

Periodic Mesoporous Organosilica Nanoparticles (PMONPs) are nanoparticles of high interest for nanomedicine applications. These nanoparticles are not composed of silica (SiO2). They belong to hybrid organic-inorganic systems. We considered using these nanoparticles for CO2 release as a contrast agent for High Intensity Focused Ultrasounds (HIFU). Three molecules (P1-P3) possessing two to four triethoxysilyl groups were synthesized through click chemistry. These molecules possess a tert-butoxycarbonyl (BOC) group whose cleavage in water at 90-100 °C releases CO2. Bis(triethoxysilyl)ethylene E was mixed with the molecules Pn (or not for P3) at a proportion of 90/10 to 75/25, and the polymerization triggered by the sol-gel procedure led to PMONPs. PMONPs were characterized by different techniques, and nanorods of 200-300 nm were obtained. These nanorods were porous at a proportion of 90/10, but non-porous at 75/25. Alternatively, molecules P3 alone led to mesoporous nanoparticles of 100 nm diameter. The BOC group was stable, but it was cleaved at pH 1 in boiling water. Molecules possessing a BOC group were successfully used for the preparation of nanoparticles for CO2 release. The BOC group was stable and we did not observe release of CO2 under HIFU at lysosomal pH of 5.5. The pH needed to be adjusted to 1 in boiling water to cleave the BOC group. Nevertheless, the concept is interesting for HIFU theranostic agents.

Porous Se@SiO2 nanospheres attenuate cisplatin-induced acute kidney injury via activation of Sirt1.

Cisplatin (CDDP) is the most commonly used chemotherapeutic drug and has an irreplaceable role in cancer treatment. However, CDDP-induced acute kidney injury (AKI) greatly limits its use. Abundant evidence has confirmed that apoptosis contributes to AKI caused by CDDP administration. The nanoparticle form of selenium, also known as Se@SiO2 nanocomposites (NPs), has been proven to be a potential agent to prevent apoptotic cell death. In this article, we established acute kidney injury models in vivo via a single injection of CDDP and used human kidney 2 (HK-2) cells for experiments in vitro. We demonstrated that NPs can improve CDDP-induced renal dysfunction. In addition, therapy with NPs attenuated apoptosis in cells and kidney tissues treated with CDDP. In terms of mechanism, we discovered that Sirt1, a deacetylase with an important role in CDDP-induced acute kidney injury, was remarkedly increased after NPs pretreatment, and the anti-apoptotic effect of the NPs was markedly abrogated after the inhibition of Sirt1. The results linked the protective effect of NPs on nephrotoxicity with Sirt1, suggesting the potential clinical importance of nanomaterials in alleviating the side effects of chemotherapy.

Effects of silica-rich water on systemic and peritoneal inflammation in rats exposed to chronic low-level (900-MHz) microwave radiation.

Immunomodulating effect of silica-rich water represents a novel field for research, especially regarding its features toward environmental pollutants. The aim of our study was to evaluate the effects of silica-rich water intake on systemic and peritoneal inflammation in rats that were chronically exposed to the low-level microwave (MW) radiation from mobile phones. Wistar Albino rats were exposed to 900 MHz MW radiation for 3 months. The four-treatment model involved rats with standard water (SW) or experimental silica-rich water intake (EW). Peritoneal macrophages (PMs) were harvested using peritoneal lavage and divided into non-stimulated and lipopolysaccharide (LPS) stimulated subgroups. The MW-exposed rats with silica-rich water (MW+EW) had lower serum tumor necrosis factor α (TNF-α) and interleukin 2 (IL-2) levels, but higher IL-10 levels, than MW+SW rats (p < 0.05). The higher TNF-α production by non-stimulated MW exposed PMs was ameliorated by the silica-rich water (p < 0.01). The MW exposition suppressed LPS potential for TNF-α synthesis in both water type groups, with greater suppression in animals that took standard water. Our results show the modulating effect of silica-rich water toward MW-induced systemic and peritoneal inflammation, which reflects the water ability to shape monocyte plasticity, thereby altering the balance between their proinflammatory and anti-inflammatory properties.