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.

Yangqing Chenfei formula alleviates crystalline silica induced pulmonary inflammation and fibrosis by suppressing macrophage polarization.

OBJECTIVE: To explore the underlying mechanisms of the effects of Yangqing Chenfei formula (, YCF) on inflammation and fibrosis in silicosis via inhibition of macrophage polarization. METHODS: A silicotic rat model was established via a single intratracheal instillation of silica particles on the first day of week 0. Subsequently, YCF was administered intragastrically to silicotic rats during weeks 0-2 and 5-8 twice daily. The mouse-derived alveolar macrophage cell line was used to investigate the mechanisms of YCF in M1/M2 polarization. RESULTS: YCF treatment effectively inhibited lung pathological changes, including inflammatory cell infiltration and tissue damage, and increased the forced expiratory volume in the first 0.3 s, functional residual capacity, and maximal mid-expiratory flow in weeks 2 and 8. Furthermore, the treatment improved lung functions by upregulating tidal volume, pause increase, and expiratory flow at 50% tidal volume from weeks 5 to 8. Moreover, YCF could significantly suppressed the progression of inflammation and fibrosis, by reducing the levels of inflammatory cytokines, as well as collagen- I and III. YCF treatment also decreased the numbers of macrophages and M1/M2 macrophages and the level of transforming growth factor-ß (TGF-ß). Additionally, YCF5, the effective substance in YCF, decreased lipopolysaccharide and interferon-γ-induced M1 macrophage polarization in a concentration-dependent manner. The mechanism of anti-M1 polarization might be related to a decrease in extracellular signal-regulated kinase, c-JUN N-terminal kinase, P38, and P65 phosphorylation. Furthermore, YCF5 inhibited interleukin-4-induced M2 macrophages by decreasing the protein and mRNA expressions of arginase-1 and CD206 as well as the levels of profibrotic factors, such as TGF-ß and connective tissue growth factor. The mechanisms underlying the anti-M2 polarization of YCF5 were primarily associated with the inhibition of the nuclear translocation of phosphorylated signal transducer and activator of transcription 6 (p-STAT6). CONCLUSION: YCF significantly inhibits inflammation and fibrosis in silicotic rats probably via the suppression of M1/M2 macrophage polarization mediated by the inhibition of mitogen-activated protein kinase and nuclear factor kappa B signaling pathways and Janus kinase/STAT6 pathways.

Delivery of miR-3529-3p using MnO2 -SiO2 -APTES nanoparticles combined with phototherapy suppresses lung adenocarcinoma progression by targeting HIGD1A.

BACKGROUND: The present study aimed to investigate the function of miR-3529-3p in lung adenocarcinoma and MnO2 -SiO2 -APTES (MSA) as a promising multifunctional delivery agent for lung adenocarcinoma therapy. METHODS: Expression levels of miR-3529-3p were evaluated in lung carcinoma cells and tissues by qRT-PCR. The effects of miR-3529-3p on apoptosis, proliferation, metastasis and neovascularization were assessed by CCK-8, FACS, transwell and wound healing assays, tube formation and xenografts experiments. Luciferase reporter assays, western blot, qRT-PCR and mitochondrial complex assay were used to determine the targeting relationship between miR-3529-3p and hypoxia-inducible gene domain family member 1A (HIGD1A). MSA was fabricated using MnO2 nanoflowers, and its heating curves, temperature curves, IC50, and delivery efficiency were examined. The hypoxia and reactive oxygen species (ROS) production was investigated by nitro reductase probing, DCFH-DA staining and FACS. RESULTS: MiR-3529-3p expression was reduced in lung carcinoma tissues and cells. Transfection of miR-3529-3p could promote apoptosis and suppress cell proliferation, migration and angiogenesis. As a target of miR-3529-3p, HIGD1A expression was downregulated, through which miR-3529-3p could disrupt the activities of complexes III and IV of the respiratory chain. The multifunctional nanoparticle MSA could not only efficiently deliver miR-3529-3p into cells, but also enhance the antitumor function of miR-3529-3p. The underlying mechanism may be that MSA alleviates hypoxia and has synergistic effects in cellular ROS promotion with miR-3529-3p. CONCLUSIONS: Our results establish the antioncogenic role of miR-3529-3p, and demonstrate that miR-3529-3p delivered by MSA has enhanced tumor suppressive effects, probably through elevating ROS production and thermogenesis.

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.

Shedding light on silica biomineralization by comparative analysis of the silica-associated proteomes from three diatom species.

Morphogenesis of the intricate patterns of diatom silica cell walls is a protein-guided process, yet to date only very few such silica biomineralization proteins have been identified. Therefore, it is currently unknown whether all diatoms share conserved proteins of a basal silica forming machinery, and whether unique proteins are responsible for the morphogenesis of species-specific silica patterns. To answer these questions, we extracted proteins from the silica of three diatom species (Thalassiosira pseudonana, Thalassiosira oceanica, and Cyclotella cryptica) by complete demineralization of the cell walls. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis of the extracts identified 92 proteins that we name 'soluble silicome proteins' (SSPs). Surprisingly, no SSPs are common to all three species, and most SSPs showed very low similarity to one another in sequence alignments. In-depth bioinformatics analyses revealed that SSPs could be grouped into distinct classes based on short unconventional sequence motifs whose functions are yet unknown. The results from the in vivo localization of selected SSPs indicates that proteins, which lack sequence homology but share unconventional sequence motifs may exert similar functions in the morphogenesis of the diatom silica cell wall.

Structural evidence for extracellular silica formation by diatoms.

The silica cell wall of diatoms, a widespread group of unicellular microalgae, is an exquisite example for the ability of organisms to finely sculpt minerals under strict biological control. The prevailing paradigm for diatom silicification is that this is invariably an intracellular process, occurring inside specialized silica deposition vesicles that are responsible for silica precipitation and morphogenesis. Here, we study the formation of long silicified extensions that characterize many diatom species. We use cryo-electron tomography to image silica formation in situ, in 3D, and at a nanometer-scale resolution. Remarkably, our data suggest that, contradictory to the ruling paradigm, these intricate structures form outside the cytoplasm. In addition, the formation of these silica extensions is halted at low silicon concentrations that still support the formation of other cell wall elements, further alluding to a different silicification mechanism. The identification of this unconventional strategy expands the suite of mechanisms that diatoms use for silicification.

The biological synthesis of gold/perlite nanocomposite using Urtica dioica extract and its chitosan-capped derivative for healing wounds infected with methicillin-resistant Staphylococcus aureus.

The preparation of ointments from natural compounds is essential for accelerating infected wounds. This study investigated the effects of topical uses of gold nanoparticles (Au)/perlite (Au/Perl) nanocomposites (NCs) by the help of Urtica dioica extract and its chitosan-capped derivative (Chit) on methicillin-resistant Staphylococcus aureus (MRSA)-infected wound healing in a mouse model. Furthermore, Au/Perl/Chit nanocomposite was prepared using protonated chitosan solution. The physicochemical properties of the as-synthesized nanocomposites were also investigated. The effects of Au/Perl/Chit NC were assessed by antibacterial, histopathological parameters as well as molecular evaluations. Then, they were compared with synthetic agent of mupirocin. The results revealed that Au/Perl NC was mesoporous and spherical in a range of 13-15 nm. Topical administration of Au/Perl/Chit ointment accelerated wound healing by reducing bacteria colonization and wound rate enhancing collagen biosynthesis and re-epithelialization, the expressions of IL-10, PI3K, AKT, bFGF, and COL1A genes, which is in agreement with the obtained results for mupirocin. In conclusion, the results strongly demonstrated that administration of ointments prepared from Au/Perl and Au/Perl/Chit nanocomposites stimulates MRSA-infected wound healing by decreasing the length of healing time and regulating PI3K/AKT/bFGF signaling pathway and is a promising candidate in stimulating MRSA-infected wound regeneration.

Lipid-Encapsulated Silica Nanobowls as an Efficient and Versatile DNA Delivery System.

Nonmesoporous Janus silica nanobowls (NBs) are unique in that they possess two different nonporous surfaces per particle for loading biological molecules and can thus be designed with multifunctional properties. Although silica NBs have been successfully employed for both targeted therapeutic and diagnostic applications, their ability to deliver DNA has not yet been fully explored. The purpose of this study was to design and develop an in vitro transfection agent that would exploit the distinct characteristics of the silica NB. First, we determined that the NB surface can be linked to either supercoiled cDNA plasmids or vectorless, linear cDNA constructs. Additionally, the linearized cDNA can be functionalized and chemisorbed on NBs to obtain a controlled release. Second, the successful transfection of cells studied was dependent on lipid coating of the NB (LNBs). Although both NBs and LNBs were capable of undergoing endocytosis, NBs appeared to remain within vesicles as shown by transmission electron microscopy (TEM). Third, fluorescence microscopy and Western blotting assays revealed that transfection of four different cell lines and acutely isolated rat sensory neurons with LNBs loaded with either linear or supercoiled cDNA constructs coding for the fluorescent protein, clover and tdTomato, resulted in protein expression. Fourth, two separate opioid receptor-ion channel signaling pathways were functionally reconstituted in HEK cells transfected with LNBs loaded with three separate cDNA constructs. Overall, these results lay the foundation for the use and further development of LNBs as in vitro transfection agents.

Omega-3 Docosahexaenoic Acid (DHA) Impedes Silica-Induced Macrophage Corpse Accumulation by Attenuating Cell Death and Potentiating Efferocytosis.

Airway exposure of lupus-prone NZBWF1 mice to crystalline silica (cSiO2), a known trigger of human autoimmune disease, elicits sterile inflammation and alveolar macrophage death in the lung that, in turn, induces early autoimmune onset and accelerates lupus progression to fatal glomerulonephritis. Dietary supplementation with docosahexaenoic acid (DHA), a marine ω-3 polyunsaturated fatty acid (PUFA), markedly ameliorates cSiO2-triggered pulmonary, systemic, and renal manifestations of lupus. Here, we tested the hypothesis that DHA influences both cSiO2-induced death and efferocytotic clearance of resultant cell corpses using three murine macrophage models: (i) primary alveolar macrophages (AM) isolated from NZBWF1 mice; (ii) self-renewing AM-like Max Planck Institute (MPI) cells isolated from fetuses of C57BL/6 mice, and (iii) RAW 264.7 murine macrophages, a virus-transformed cell line derived from BALB/c mice stably transfected with the inflammasome adaptor protein ASC (RAW-ASC). Incubation with cSiO2 at 25 and 50 µg/ml for 6 h was found to dose-dependently induce cell death (p < 0.05) in all three models as determined by both acridine orange/propidium iodide staining and release of lactate dehydrogenase into cell culture supernatant. Pre-incubation with DHA at a physiologically relevant concentration (25 µM) significantly reduced cSiO2-induced death (p < 0.05) in all three models. Cell death induction by cSiO2 alone and its suppression by DHA were primarily associated with caspase-3/7 activation, suggestive of apoptosis, in AM, MPI, and RAW-ASC cells. Fluorescence microscopy revealed that all three macrophage models were similarly capable of efferocytosing RAW-ASC target cell corpses. Furthermore, MPI effector cells could likewise engulf RAW-ASC target cell corpses elicited by treatment with staurosporine (apoptosis), LPS, and nigericin (pyroptosis), or cSiO2. Pre-incubation of RAW-ASC target cells with 25 µM DHA prior to death induced by these agents significantly enhanced their efferocytosis (p < 0.05) by MPI effector cells. In contrast, pre-incubating MPI effector cells with DHA did not affect engulfment of RAW-ASC target cells pre-incubated with vehicle. Taken together, these findings indicate that DHA at a physiologically relevant concentration was capable of attenuating macrophage death and could potentiate efferocytosis, with the net effect of reducing accumulation of cell corpses capable of eliciting autoimmunity.

Visualising Silicon in Plants: Histochemistry, Silica Sculptures and Elemental Imaging.

Silicon is a non-essential element for plants and is available in biota as silicic acid. Its presence has been associated with a general improvement of plant vigour and response to exogenous stresses. Plants accumulate silicon in their tissues as amorphous silica and cell walls are preferential sites. While several papers have been published on the mitigatory effects that silicon has on plants under stress, there has been less research on imaging silicon in plant tissues. Imaging offers important complementary results to molecular data, since it provides spatial information. Herein, the focus is on histochemistry coupled to optical microscopy, fluorescence and scanning electron microscopy of microwave acid extracted plant silica, techniques based on particle-induced X-ray emission, X-ray fluorescence spectrometry and mass spectrometry imaging (NanoSIMS). Sample preparation procedures will not be discussed in detail, as several reviews have already treated this subject extensively. We focus instead on the information that each technique provides by offering, for each imaging approach, examples from both silicifiers (giant horsetail and rice) and non-accumulators (Cannabis sativa L.).

Hyperthermia-triggered UK release nanovectors for deep venous thrombosis therapy.

Deep vein thrombosis (DVT) is a common and lethal complication of surgery. In the clinic, thrombolytic drugs are primarily used for treating DVT. However, the utilization of thrombolytic drugs is limited due to the risk of urokinase (UK)-related hemorrhagic complications. In this paper, a binary eutectic phase-change fatty acid composed of lauric acid and stearic acid was used to block the pores of gold-mesoporous silica core-shell nanoparticles, so as to deliver thrombolytic drugs. The eutectic mixture has a well-defined melting point at 39.2 °C, which can be used as a biocompatible phase-change material for hyperthermia-triggered drug release. The prepared system presents remarkable photothermal effects due to the gold nanoparticles and quick drug release in response to near-infrared irradiation (NIR). In addition, localized hyperthermia could also enhance the lysis of the thrombus. The thrombolytic effect of this system was evaluated in vitro and in vivo. Herein, a rabbit femoral vein thrombosis model was first built for imitating thrombolysis in vivo. The B-ultrasound was then used to monitor the changes in the thrombus after treatment. The results indicated that the reported system could be potentially used to deliver thrombotic drugs in the clinic.

Modulation of secondary metabolite profiles by biologically synthesized MgO/perlite nanocomposites in Melissa officinalis plant organ cultures.

In this work, biological synthesis of MgO/perlite nanocomposites (NCs) besides their effects on morphology and secondary metabolite profiles of Melissa officinalis plant organ cultures were evaluated. MgO NPs were immobilized on the surface of nanoperlite using M. officinalis extract as a capping agent. The as-synthesized MgO/perlite NCs were characterized by using FTIR, XRD, SEM, EDS and DLS. The average particle size of nanoperlite and MgO/perlite NCs was about 10 and 30 nm, respectively. Morphological observations showed that nanoperlite and MgO/perlite NCs had no effect on root number, as well as root and shoot length. None of the applied concentrations of perlite and MgO/perlite NCs could significantly increase the growth parameters in comparison to the control, except for 150 mg/L of nanoperlite which caused an increase in the shoot number. Although, the contents of chlorophyll and carotenoids were not affected, the maximum content of volatile compounds obtained at 100 of MgO/perlite NCs. Rosmarinic acid was detected in shoots, which treated with 25-100 mg/L of perlite and 25, 50 and 150 mg/L of MgO/perlite NCs. Our results provided the evidence that nanoperlite and MgO/perlite NCs at specific levels may act as a novel elicitor for in vitro biosynthesis of valuable secondary metabolites.

Bioavailability Enhancement of Aripiprazole Via Silicosan Particles: Preparation, Characterization and In vivo Evaluation.

The aim of this study was to design a novel carrier for enhancing the bioavailability of the poorly water-soluble drug, aripiprazole (ARP). Silicosan, the applied carrier, was obtained by chemical interaction between tetraethyl orthosilicate (TEOS) and chitosan HCl. Different ARP-loaded silicosan particles were successfully prepared in absence and presence of one of the following surfactants; Tween 80, Poloxamer 407 and cetyltrimethylammonium bromide (CTAB). The prepared ARP-loaded silicosan particles were thoroughly investigated for their structures using FTIR, XRD, and DSC analysis as well as their particle size, zeta potential, flowability, drug content, and in vitro drug release efficiencies. The prepared ARP-loaded silicosan particles were characterized by amorphous structure, high drug entrapment efficiency and a remarkable improvement in the release of aripiprazole in simulated gastric fluid. SEM and EDX revealed that the morphology and silica atom content in the prepared ARP-loaded silicosan particles were affected by the used surfactant in their formulations. The selected ARP-loaded silicosan particles were subjected to in vivo study using rabbits. The obtained pharmacokinetic results showed that the relative bioavailability for orally administered ARP-loaded silicosan particles (SC-2-CTAB) was 66% higher relative to the oral suspension (AUC0-10h was 16.38 ± 3.21 and 27.23 ± 2.35 ng.h/mL for drug powder and SC-2-CTAB formulation, respectively). The obtained results suggested the unique-structured silicosan particles to be used as successful vehicle for ARP.

Elemental and macromolecular modifications in Triticum aestivum L. plantlets under different cultivation conditions.

Young wheat plantlets (wheatgrass), represent a significant source of minerals, enzymes, vitamins, while also rich in phenolics and chlorophylls, with considerable bioactivities. As the biosynthesis of such compounds may be influenced by growth conditions, the current research assesses wheatgrass composition in soil based and hydroponic systems, using water with different elemental composition. FTIR spectroscopy did not reveal significant variations between juice and extracts cultivated in different setups. Surface elemental composition indicated higher Na, P, Si concentrations in hydroponic plants, while AAS analyses showed increased Ca and Mn in soil presence. HPLC-MS of extracts showed that soil and spring water increased chlorophyll and hydroxychlorophyll a concentrations. Phenolic contents were higher in hydroponic plants, while maximum values were recorded for spring water. Radical scavenging activity was stimulated by the use of spring water. Results indicate that wheatgrass with improved mineral and macromolecular composition may be obtained using accessible cultivation setups.

Telomerase Responsive Delivery of Doxorubicin from Mesoporous Silica Nanoparticles in Multiple Malignancies: Therapeutic Efficacies against Experimental Aggressive Murine Lymphoma.

Mammalian telomerase maintains the length and integrity of telomeres by adding the telomeric repeats to the chromosome end. This work describes the telomerase responsive delivery of doxorubicin against telomerase positive human and murine cancer cells. Wrapping of doxorubicin loaded mesoporous silica nanoparticles with specific oligonucleotide sequence, containing telomeric repeat complementary sequence and a telomerase substrate primer sequence, resulted in slow and sustained release of doxorubicin, contiguous to the tumor cells. The DNA wrapped nanoprobe significantly inhibits the proliferation and enhanced the cytotoxicity in telomerase positive human and mouse tumor cells, and its function is impeded following exposure to specific telomerase inhibitor, AZT. Entrapping of doxorubicin by telomerase specific oligo manifests enhanced apoptosis and significantly higher uptake of the drug in the tumor cells. Treatment of telomerase positive Dalton's lymphoma bearing mice with a novel and newly designed oligo wrapped nanoprobe, specific for mouse telomerase, significantly enhanced the survival and improved the histopathological parameters. In addition, the treatment also induced significant reduction in the number of tumor foci and restored the normal architecture of the vascularized organs, besides preventing metastasis.

Cytotoxicity, genotoxicity, transplacental transfer and tissue disposition in pregnant rats mediated by nanoparticles: the case of magnetic core mesoporous silica nanoparticles.

Whether in the cosmetic or as therapeutic, the use of nanoparticles has been increasing and taking on global proportion. However, there are few studies about the physical potential of long-term use or use in special conditions such as chronic, AIDS, pregnant women and other special health circumstances. In this context, the study of the mutagenicity and the transplacental passage represents an important and reliable model for the primary evaluation of potential health risks, especially maternal and child health. In this study we performed mutagenicity, cytotoxic and transplacental evaluation of magnetic core mesoporous silica nanoparticles, radiolabeled with 99mTc for determination of toxicogenic and embryonic/fetuses potential risk in animal model. Magnetic core mesoporous silica nanoparticles were produced and characterized by obtaining nanoparticles with a size of (58.9 ± 8.1 nm) in spherical shape and with intact magnetic core. The 99 m Tc radiolabeling process demonstrated high efficacy and stability in 98% yield over a period of 8 hours of stability. Mutagenicity assays were performed using Salmonella enteric serovar Typhimurium standard strains TA98, TA100 and TA102. Cytotoxicity assays were performed using WST-1. The transplacental evaluation assays were performed using the in vivo model with rats in two periods: embryonic and fetal stage. The results of both analyzes corroborate that the nanoparticles can i) generate DNA damage; ii) generate cytotoxic potential and iii) cross the transplantation barrier in both stages and bioaccumulates in both embryos and fetuses. The results suggest that complementary evaluations should be conducted in order to attest safety, efficacy and quality of nanoparticles before unrestricted approval of their use.

Dynamic analysis of the interactions between Si/SiO2 quantum dots and biomolecules for improving applications based on nano-bio interfaces.

Due to their outstanding properties, quantum dots (QDs) received a growing interest in the biomedical field, but it is of major importance to investigate and to understand their interaction with the biomolecules. We examined the stability of silicon QDs and the time evolution of QDs - protein corona formation in various biological media (bovine serum albumin, cell culture medium without or supplemented with 10% fetal bovine serum-FBS). Changes in the secondary structure of BSA were also investigated over time. Hydrodynamic size and zeta potential measurements showed an evolution in time indicating the nanoparticle-protein interaction. The protein corona formation was also dependent on time, albumin adsorption reaching the peak level after 1 hour. The silicon QDs adsorbed an important amount of FBS proteins from the first 5 minutes of incubation that was maintained for the next 8 hours, and diminished afterwards. Under protein-free conditions the QDs induced cell membrane damage in a time-dependent manner, however the presence of serum proteins attenuated their hemolytic activity and maintained the integrity of phosphatidylcholine layer. This study provides useful insights regarding the dynamics of BSA adsorption and interaction of silicon QDs with proteins and lipids, in order to understand the role of QDs biocorona.

Optical microalgal biosensors for aqueous contaminants using organically doped silica as cellular hosts.

Optical biosensors for the detection of toxic species in aqueous media were developed via the encapsulation of microalgae in sol-gel matrices. In a first step, the effect of cadmium(II), lead(II), and anthracene on the chlorophyll a fluorescence intensity of Anabaena flos-aquae, Chlorella vulgaris, and Euglena gracilis microalgae in suspension was studied. Complementary ATP-metry measurements demonstrated a direct relationship between optical response and pollutant toxicity, in a cell- and dose-dependent manner. In a second step, microalgae were successfully encapsulated in silicate-colloidal silica nanocomposite matrices. However, a complete loss of cell response to pollutant addition was observed, despite the preservation of cell viability. Introduction of a low amount (5 mol%) of amine- or ethyl-bearing silanes in the matrix formulation allowed the recovery of the sensing capacity of the immobilized microalgae, without impacting on the response time (30 s). Porosimetry and 29Si solid-state NMR spectroscopy showed that the organic moieties are fully integrated into the inorganic network, tuning the ability of the target pollutant to diffuse and reach the encapsulated algae. This versatile strategy could be useful for the easy and fast assessment of contamination levels in polluted waters. Graphical Abstract Microalgal biosensors for aqueous contaminants using organically doped silica as cellular hosts.

Supersaturated silica-lipid hybrids (super-SLH): An improved solid-state lipid-based oral drug delivery system with enhanced drug loading.

The method of supersaturation for achieving high drug loads in lipid-based formulations is under exploited and relatively unexplored, especially in the case of solid-state lipid-based formulations. Silica-lipid hybrids are solid-state lipid-based formulations designed for improving the oral delivery of poorly water-soluble drugs. However, their application to compounds of low potency and requiring large doses is limited by their low drug loading capacity. Here, an innovative technique to fabricate supersaturated silica-lipid hybrid formulations (super-SLH) has been established and the relationship between drug load and performance investigated. Using the model poorly water-soluble drug, ibuprofen, super-SLH was fabricated possessing drug loads ranging from 8 to 44% w/w, i.e. greater than the previously developed standard ibuprofen silica-lipid hybrids (5.6% w/w). Drug crystallinity of the encapsulated ibuprofen ranged from non-crystalline to part-crystalline with an increase in drug load. Super-SLH achieved improved rates and extents of dissolution when compared to pure ibuprofen, regardless of the drug load. The percentage increase in dissolution extent at 60 min varied from 200 to 600%. The results of the current study indicate that supersaturation greatly improves drug loading and that 16-25% w/w is the optimum loading level which retains optimal dissolution behaviour for the oral delivery of ibuprofen, which has the potential to be translated to other poorly water-soluble drugs.

A study of biocatalysts based on glucose oxidase.

During this work, we studied the possibility of glucose oxidase (GOx) covalent immobilization on a modified inorganic support. A series of GOx-based biocatalysts was synthesized by crosslinking the enzyme to a surface of modified silica or alumina. Polyelectrolyte layers were used as modifiers for the silica and alumina surfaces. These layers promote tight binding of the GOx to the support. The biocatalyst's activity and stability were studied using an oxidation reaction of d-glucose to d-gluconic acid. It was found that GOx immobilized on the modified SiO2 using glutardialdehyde as a crosslinking agent was the most active and stable catalytic system, showing an 85% yield of gluconic acid. A study of the synthesized biocatalyst structure using FTIR spectroscopy showed that the enzyme was covalently crosslinked to the surface of an inorganic support modified with chitosan and glutardialdehyde. In the case of SiO2, the quantity of the immobilized enzyme was higher than in the case of Al2O3.