Organosilica Layer Research Articles

Exploring the Potential of Various Cyclodextrin-Based Derivatives in Enzyme Supramolecular Engineering.

Enzyme stability and activity are pivotal factors for their implementation in different industrial applications. Enzyme supramolecular engineering relies on the fabrication of a tailor-made enzyme nano-environment to ensure enzyme stability without impairing activity. Cyclodextrins (CDs), cyclic oligomers of glucose, act as protein chaperones and stabilize, upon interaction with hydrophobic amino acid residues exposed at the protein surface, its three-dimensional structure. When used to build an organosilica layer shielding an enzyme, they enhance the protective effect of this layer. In the present study, we systematically assessed the protective effects of three organosilane derivatives based on ɑ-, β- and γ-CDs. A model lipase enzyme was immobilized at the surface of silica nanoparticles and shielded in an organosilica layer containing these organosilanes. Besides layer thickness optimization, the effect of different stressors (i. e., temperature, SDS, urea) was tested. Our results showed that organosilica layers produced with CDs improve enzyme thermal stability. They also support enzyme refolding after denaturation under chaotic conditions. Additionally, we demonstrated that the protective effect of the smallest CD derivative tested, namely ɑ-CD, surpassed the other macrocycles studied for conferring the immobilized enzyme with higher resistance to stress conditions. This protection strategy was also applied to a thermostable β-galactosidase enzyme.

Reduction-responsive immobilised and protected enzymes.

We report a synthetic strategy to produce nano-immobilised and organosilica-shielded enzymes of which the biocatalytic activity is, by design, chemically enhanced under reductive conditions. The enzymes were immobilised onto silica nanoparticles through a reduction-responsive crosslinker and further shielded in an organosilica layer of controlled thickness. Under reducing conditions, disulphide bonds linking the protein to the carrier material were reduced, triggering enzyme activation. The organosilica shield prevents the enzymes from leaching from the nanobiocatalysts and preserves their integrity.

Development and characterization of magnetic-based biodegradable periodic mesoporous organosilica nanoparticles for enhanced biomedical applications

Herein, magnetic-based biodegradable periodic mesoporous organosilica (BPMO) nanoparticles were successfully synthesized via a co-precipitation method to form a magnetic iron oxide (Fe3O4) core, followed by the condensation of organosilica precursors to produce BPMO shells. The physicochemical properties of the resulting hybrid nanoparticles were evaluated using powder X-ray diffraction, nitrogen adsorption–desorption isotherms, thermogravimetric analysis, Fourier transform infrared spectroscopy, and vibrating sample magnetometry. The synthesized particles exhibited a spherical morphology with an average diameter of approximately 250 nm. A core–shell structure was formed by depositing a 100-nm biodegradable organosilica layer onto the magnetic Fe3O4 cluster, endowing the nanoparticles with both magnetic and biodegradable mesoporous characteristics. Notably, despite the silica coating, the saturation magnetization remained high, reaching 35.8 emu/g, suggesting the potential for using these nanoparticles in magnetic-based biomedical applications. Furthermore, Fe3O4@BPMO nanoparticles were demonstrated to be efficiently uptaken by OVCAR8 ovarian cancer cells and spheroids, indicating that these nanoparticles are promising as magnetic nanocarriers for anti-cancer drug delivery and can be used in magnetic resonance imaging and magnetic hyperthermia.

Super-assembled periodic mesoporous organosilica membranes with hierarchical channels for efficient glutathione sensing.

Bioinspired nanochannel-based sensors have elicited significant interest because of their excellent sensing performance, and robust mechanical and tunable chemical properties. However, the existing designs face limitations due to material constraints, which hamper broader application possibilities. Herein, a heteromembrane system composed of a periodic mesoporous organosilica (PMO) layer with three-dimensional (3D) network nanochannels is constructed for glutathione (GSH) detection. The unique hierarchical pore architecture provides a large surface area, abundant reaction sites and plentiful interconnected pathways for rapid ionic transport, contributing to efficient and sensitive detection. Moreover, the thioether groups in nanochannels can be selectively cleaved by GSH to generate hydrophilic thiol groups. Benefiting from the increased hydrophilic surface, the proposed sensor achieves efficient GSH detection with a detection limit of 1.2 μM by monitoring the transmembrane ionic current and shows good recovery ranges in fetal bovine serum sample detection. This work paves an avenue for designing and fabricating nanofluidic sensing systems for practical and biosensing applications.

Exploiting cyclodextrins as artificial chaperones to enhance enzyme protection through supramolecular engineering.

We report a method of enzyme stabilisation exploiting the artificial protein chaperone properties of β-cyclodextrin (β-CD) covalently embedded in an ultrathin organosilica layer. Putative interaction points of this artificial chaperone system with the surface of the selected enzyme were studied in silico using a protein energy landscape exploration simulation algorithm. We show that this enzyme shielding method allows for drastic enhancement of enzyme stability under thermal and chemical stress conditions, along with broadening the optimal temperature range of the biocatalyst. The presence of the β-CD macrocycle within the protective layer supports protein refolding after treatment with a surfactant.

Nanobiocatalysts with inbuilt cofactor recycling for oxidoreductase catalysis in organic solvents.

The major stumbling block in the implementation of oxidoreductase enzymes in continuous processes is their stark dependence on costly cofactors that are insoluble in organic solvents. We describe a chemical strategy that allows producing nanobiocatalysts, based on an oxidoreductase enzyme, that performs biocatalytic reactions in hydrophobic organic solvents without external cofactors. The chemical design relies on the use of a silica-based carrier nanoparticle, of which the porosity can be exploited to create an aqueous reservoir containing the cofactor. The nanoparticle core, possessing radial-centred pore channels, serves as a cofactor reservoir. It is further covered with a layer of reduced porosity. This layer serves as a support for the immobilisation of the selected enzyme yet allowing the diffusion of the cofactor from the nanoparticle core. The immobilised enzyme is, in turn, shielded by an organosilica layer of controlled thickness fully covering the enzyme. Such produced nanobiocatalysts are shown to catalyse the reduction of a series of relevant ketones into the corresponding secondary alcohols, also in a continuous flow fashion.

Plasmonic photothermal activation of an organosilica shielded cold-adapted lipase co-immobilised with gold nanoparticles on silica particles.

Gold nanoparticles (AuNPs), owing to their intrinsic plasmonic properties, are widely used in applications ranging from nanotechnology and nanomedicine to catalysis and bioimaging. Capitalising on the ability of AuNPs to generate nanoscale heat upon optical excitation, we designed a nanobiocatalyst with enhanced cryophilic properties. It consists of gold nanoparticles and enzyme molecules, co-immobilised onto a silica scaffold, and shielded within a nanometre-thin organosilica layer. To produce such a hybrid system, we developed and optimized a synthetic method allowing efficient AuNP covalent immobilisation on the surface of silica particles (SPs). Our procedure allows to reach a dense and homogeneous AuNP surface coverage. After enzyme co-immobilisation, a nanometre-thin organosilica layer was grown on the surface of the SPs. This layer was designed to fulfil the dual function of protecting the enzyme from the surrounding environment and allowing the confinement, at the nanometre scale, of the heat diffusing from the AuNPs after surface plasmon resonance photothermal activation. To establish this proof of concept, we used an industrially relevant lipase enzyme, namely Lipase B from Candida Antarctica (CalB). Herein, we demonstrate the possibility to photothermally activate the so-engineered enzymes at temperatures as low as -10 °C.

On the Mixed Gas Behavior of Organosilica Membranes Fabricated by Plasma-Enhanced Chemical Vapor Deposition (PECVD).

Selective, nanometer-thin organosilica layers created by plasma-enhanced chemical vapor deposition (PECVD) exhibit selective gas permeation behavior. Despite their promising pure gas performance, published data with regard to mixed gas behavior are still severely lacking. This study endeavors to close this gap by investigating the pure and mixed gas behavior depending on temperatures from 0 °C to 60 °C for four gases (helium, methane, carbon dioxide, and nitrogen) and water vapor. For the two permanent gases, helium and methane, the studied organosilica membrane shows a substantial increase in selectivity from αHe/CH4 = 9 at 0 °C to αHe/CH4 = 40 at 60 °C for pure as well as mixed gases with helium permeance of up to 300 GPU. In contrast, a condensable gas such as CO2 leads to a decrease in selectivity and an increase in permeance compared to its pure gas performance. When water vapor is present in the feed gas, the organosilica membrane shows even stronger deviations from pure gas behavior with a permeance loss of about 60 % accompanied by an increase in ideal selectivity αHe/CO2 from 8 to 13. All in all, the studied organosilica membrane shows very promising results for mixed gases. Especially for elevated temperatures, there is a high potential for separation by size exclusion.

Long alkyl chain-containing organosilica/silicalite-1 composite membranes for alcohol recovery

A long alkyl chain-containing organosilica layer obtained from 1, 8-bis(triethoxysilyl)octane (BTESO) was used to modify silicalite-1 membranes via a sol−gel method to obtain bi-layered BTESO/silicalite-1 composite membranes on macroporous α-Al2O3 supports for the recovery of diluted ethanol by pervaporation. Silicalite-1 zeolite membranes were hydrothermally synthesized using two seeding methods: those prepared using wet−rubbing seeding method exhibited larger separation factors than those obtained using the dip−coating method in the pervaporation of ethanol/water due to the thinner seed layer in the former. After modified with BTESO, the surface became smoother and denser with higher hydrophobicity, and the thickness of BTESO layer was approximately 300 nm on both types of membranes. In pervaporation, two types of silicalite-1 membranes unexpectedly showed similar performances after BTESO modification. Ethanol flux increased or was maintained while water flux decreased greatly for silicalite-1 membranes after BTESO coating with increasing sol concentrations, and a higher separation factor was attained without sacrificing ethanol flux. The long alkyl chains in BTESO and silanols reacted with hydroxyl groups in silicalite-1 provided flexibility and hydrophobicity for ethanol transport with minor resistance. The optimized 2.0% BTESO/silicalite-1 membranes synthesized using wet−rubbing method showed a maximum flux of 6.84 kg m−2 h−1 and separation factor of 24.6 with overall pervaporation separation index of 161 in the pervaporation of 5.0 wt% ethanol/water mixture at 60 °C.

Immobilisation and stabilisation of glycosylated enzymes on boronic acid-functionalised silica nanoparticles.

We report a method of glycosylated enzymes' surface immobilisation and stabilisation. The enzyme is immobilised at the surface of silica nanoparticles through the reversible covalent binding of vicinal diols of the enzyme glycans with a surface-attached boronate derivative. A soft organosilica layer of controlled thickness is grown at the silica surface, entrapping the enzyme and thus avoiding enzyme leaching. We demonstrate that this approach results not only in high and durable activity retention but also enzyme stabilisation.

Alginate Lyase Guided Silver Nanocomposites for Eradicating Pseudomonas aeruginosa from Lungs.

Pseudomonas aeruginosa (P. aeruginosa) infections lead to a high mortality rate for cystic fibrosis or immunocompromised patients. The alginate of the biofilm was believed to be the key factor disabling immune therapy and antibiotic treatments. A silver nanocomposite consisting of silver nanoparticles and a mesoporous organosilica layer was created to deliver two pharmaceutical compounds (alginate lyase and ceftazidime) to degrade the alginate and eradicate P. aeruginosa from the lungs. The introduction of thioether-bridged mesoporous organosilica into the nanocomposites greatly benefited the conjunction of foreign functional molecules such as alginate lyase and increased their hemocompatibility and drug-loading capacity. Silver nanocomposites with a uniform diameter (∼39 nm) exhibited a high dispersity, good biocompatibility, and high ceftazidime-loading capacity (380.96 mg/g). Notably, the silver nanocomposites displayed a low pH-dependent drug release and degradation profiles (pH 6.4), guaranteeing the targeted release of the drugs in the acidic niches of the P. aeruginosa biofilm. Indeed, particles loaded with alginate lyase and ceftazidime exhibited high inhibitory and degradation effects on the biofilm of P. aeruginosa PAO1 based on the specific catalytic activity of the enzyme to the alginate and antibacterial function of their loaded ceftazidime and silver ions. It should be noted that the enzyme-decorated nanocomposites succeeded in eradicating P. aeruginosa PAO1 from the mouse lungs and decreasing the lung injuries. No deaths or serious side effects were observed during the experiments. We believe that the silver nanocomposites with high biocompatibility and organic group-incorporated framework have the potential to be used to deliver multiple functional molecules for antibacterial therapy in clinical application.

Refreshable Nanobiosensor Based on Organosilica Encapsulation of Biorecognition Elements.

Implantable and wearable biosensors that enable monitoring of biophysical and biochemical parameters over long durations are highly attractive for early and presymptomatic diagnosis of pathological conditions and timely clinical intervention. Poor stability of antibodies used as biorecognition elements and the lack of effective methods to refresh the biosensors upon demand without severely compromising the functionality of the biosensor remain significant challenges in realizing protein biosensors for long-term monitoring. Here, we introduce a novel method involving organosilica encapsulation of antibodies for preserving their biorecognition capability under harsh conditions, typically encountered during the sensor refreshing process, and elevated temperature. Specifically, a simple aqueous rinsing step using sodium dodecyl sulfate (SDS) solution refreshes the biosensor by dissociating the antibody-antigen interactions. Encapsulation of the antibodies with an organosilica layer is shown to preserve the biorecognition capability of otherwise unstable antibodies during the SDS treatment, thus ultimately facilitating the refreshability of the biosensor over multiple cycles. Harnessing this method, we demonstrate the refreshability of plasmonic biosensors for anti-IgG (model bioanalyte) and neutrophil gelatinase-associated lipocalin (NGAL) (a biomarker for acute and chronic kidney injury). The novel encapsulation approach demonstrated can be easily extended to other transduction platforms to realize refreshable biosensors for monitoring of protein biomarkers over long durations.

Enzyme Shielding in an Enzyme-thin and Soft Organosilica Layer

Enzyme Shielding in an Enzyme-thin and Soft Organosilica Layer

A simple way to prepare a hydrophobic Sr[LiAl3N4]:Eu2+ phosphor with improved moisture resistance

The red-emitting Sr[LiAl3N4]:Eu2+ (SLA) phosphor was synthesized under flowing N2 gas. A thin organosilica layer (about 5–10 nm) was coated on the surface of SLA phosphors by a very simple method, which transformed the phosphor surface from hydrophilicity to hydrophobicity. The contact angle of water droplets on the surface of the packed SLA phosphors was more than 140°. Compared with the unmodified sample, the modified SLA phosphors could keep at a high emission intensity for more than twice the time under an extremely high moisture level (at relative humidity of 100%, 85 °C). The hydrophobic modification could also improve the uniform dispersion of phosphors during assembly process of white LED.

Shielding of Enzyme by a Stable and Protective Organosilica Layer on Monolithic Scaffolds for Continuous Bioconversion

In this study, a kind of robust monolithic biocatalyst was constructed through shielding enzymes on the surface of cordierite honeycomb (cordierite-H) ceramics with an organosilica layer. In brief, penicillin G acylase, as a typical enzyme, was immobilized on the cordierite-H surface modified with polydopamine. Then, an organosilica layer was formed through the sol–gel process with (3-aminopropyl)tetraethoxysilane and tetraethyl orthosilicate. The buffering effect of the organosilica and polydopamine layer as well as the cage effect of the organosilica layer could effectively protect the enzyme from denaturation and detachment, thus significantly improving its structural and operational stability. A fixed-bed reactor containing the above monolithic biocatalysts was then constructed. The enzyme could retain up to 89.7% of its initial activity after a 195 min reaction at 313 K and 73.1% of its initial activity after 15 reaction cycles. Furthermore, continuous bioconversion of penicillin G potassium was also achieved, with a final product yield of 41.8% after five cycles of reaction.

(Invited) Narrow Band Emission of Nitrides Phosphors and All Inorganic Perovskite Quantum Dots for the Application in Light Emitting Diodes

A narrow band emission nitride SrLiAl3N4:Eu2+ (SLA) red phosphor prepared through a high-pressure solid state reaction was coated with organosilica layers in 400 ~ 600 nm thickness to improve its waterproof property. The coated samples showed excellent moisture resistance while retaining an external quantum efficiency (EQE) of 70% of its initial EQE after being aged for 5 days in harsh conditions. White light-emitting diodes (LEDs) of SLA red-phosphors and commercial Y3Al5O12:Ce3+ (YAG:Ce) yellow-phosphor on a blue-InGaN chip were shown high color rendition (CRI = 89, R9 = 69) and low correlated color temperature of 2406 K. All-inorganic CsPbX3 (X = Cl, Br, I) perovskite quantum dots (PQDs) with narrow emission bad were synthesized by hot injection methods. We propose an efficient and simple method to prevent the anion-exchange effect. We mixed green CsPbBr3 PQDs with purchased mesoporous silica. We applied the new PQD-based LEDs for backlight displays. Our white LED device for backlight display passed through a color filter with an NTSC value of 113% and Rec. 2020 of 85%. For lighting application, we used red perovskite quantum dots assisted by a yellow YAG:Ce phosphor were integrated on a blue chip. This warm white light with CCT (3328K), high color rendering index (CRI = 84.7) and a super high value of saturated red color component R9 as 96. Nitrides phosphors and all inorganic quantum dots were a good candidate for the application of white light LEDs with narrow emission band.

Engineering Nanosized Organosilica for Molecular Recognition and Biocatalysis Applications.

A series of synthetic nanomaterials capable of molecular recognition and/or biocatalysis have been produced by exploiting the self-sorting, self-assembly and polycondensation of organosilane building blocks around protein templates. The established methodology allows for the production of thin organosilica layers of controlled thickness, down to nanometer precision. Fully synthetic virus recognition materials have been shown to specifically bind their target virus down to picomolar concentrations. The shielding of natural enzymes allowed producing nanobiocatalysts functioning under harsh operational conditions.

Relaxometric property of organosilica nanoparticles internally functionalized with iron oxide and fluorescent dye for multimodal imaging

Multimodal imaging using novel multifunctional nanoparticles provides a new approach for the biomedical field. Thiol-organosilica nanoparticles containing iron oxide magnetic nanoparticles (MNPs) as the core and rhodamine B in the thiol-organosilica layer (thiol OS-MNP/Rho) were synthesized in a one-pot process. The thiol OS-MNP/Rho showed enhanced magnetic resonance imaging (MRI) contrast and high fluorescence intensity. The relaxometry of thiol OS-MNP/Rho revealed a novel coating effect of the organosilica layer to the MNPs. The organosilica layer shortened the T2 relaxation time but not the T1 relaxation time of the MNPs. We injected thiol-OS-MNP/Rho into normal mice intravenously. Injected mice revealed an alteration of the liver contrast in the MRI and a fluorescent pattern based on the liver histological structure at the level between macroscopic and microscopic fluorescent imaging (mesoscopic FI). In addition, the labeled macrophages were observed at the single cell level histologically. We demonstrated a new approach to evaluate the liver at the macroscopic, microscopic level as well as the mesoscopic level using multimodal imaging.

Enzyme Armoring by an Organosilica Layer: Synthesis and Characterization of Hybrid Organic/Inorganic Nanobiocatalysts.

The availability of highly stable and reusable enzymes is one of the main challenges in bio-based industrial processes. Enzyme immobilization and encapsulation represent promising strategies to reach this goal. In this chapter, the synthetic strategy to produce hybrid organic/inorganic nanobiocatalysts (NBC) is reported. This strategy is based on the sequential immobilization of an enzyme on the surface of silica nanoparticles followed by the growth, at the surface of the nanoparticles, of a shielding layer which serves as an armor to protect the enzyme against denaturation/degradation. This armor is produced through a thickness-controlled organosilane poly-condensation onto the nanoparticle surface around the enzyme to form a protective organosilica layer. The armored nanobiocatalysts present enhanced catalytic activity and improved stability against heat, pH, chaotropic agents, proteases, and ultrasound. The method is versatile in that it can be successfully adapted to a number of different enzymes.

Imaging of carotid artery inflammatory plaques with superparamagnetic nanoparticles and an external magnet collar.

Stroke is one of the top three fatal diseases in human history. Inflammatory injury of the artery endo-membrane system is widely accepted as the major starting mechanism for the formation and enlargement of atherosclerosis plaque, which can be diagnosed by B-ultrasound or carotid angiography. However, clinical data reveal that there are asymptomatic patients that are not diagnosed until the stenosis degree is over 70%. Superparamagnetic iron oxide (SPIO), a promising candidate for a next generation contrast agent in medical imaging, has been used in the imaging of carotid artery plaques, but it still faces the challenge of targeted enrichment. Herein, we introduce a mature magnetic nanoparticle contrast agent and a promising method for diagnosing carotid artery inflammatory plaques with a Magnetic Resonance Imaging (MRI) technique. The superparamagnetic nanoparticles (SNPs) were synthesized by directly coating hydrophilic and high-magnetism Fe3O4 nanoparticles with an organosilica layer, which was followed by modification with polyethylene glycol. It was verified that the resultant nanocomposite possesses a higher structural stability, excellent dispersivity, separability, as well as biosafety. More importantly, the strong magnetism was preserved, making it possible to attract the SNPs with an external magnetic field and achieve a target concentration within the lesion. Moreover, an in vitro magnetic collar, designed to produce a stable magnetic field around the superficial common carotid arteries was introduced. The SNPs particles in the blood flow were slowed down by the collar, their motion direction was changed, and they were captured by the inflammatory cells in the plaque. The effectiveness and feasibility of the particles were evaluated via testing the MRI performance on histological levels with a rat carotid plaque model. The SNPs that were concentrated and accumulated in the plaque were verified to present an evident, negative enhancement in the Proton Density-T2 (PD-T2) sequence images. Therefore, it was demonstrated that the superparamagnetic nanoparticles have great potential as an MRI contrast agent to detect early stage carotid artery inflammatory plaques with an external magnetic collar.