Shell Silica Nanoparticles Research Articles

Controlling Surface Chemical Heterogeneities of Ultrasmall Fluorescent Core–Shell Silica Nanoparticles as Revealed by High-Performance Liquid Chromatography

Ultrasmall (diameter below 10 nm) fluorescent core–shell silica nanoparticles have garnered increasing attention in recent years as a result of their high brightness and favorable biodistribution p...

Optimization of gold core-mesoporous silica shell functionalization with TPGS and PEI for cancer therapy

Photothermal therapy (PTT) has captured the attention of different researchers around the world, since the application of NIR light responsive-nanomaterials has shown promising results in cancer therapy. Gold-core mesoporous silica shell (Au-MSS) nanoparticles allow the combination of gold mediated PTT with the drug delivery in order to improve their therapeutic potential. In this study, two different methodologies, electrostatic or chemical linkage, were explored to functionalize Au-MSS nanorods with TPGS and PEI. For that purpose, the TPGS and PEI were chemically coupled to each other or modified with 3-(triethoxysilyl)propyl isocyanate. The produced Au-MSS nanorods display a uniform morphology and a well-defined gold nucleus and silica shell. Further, the particles surface charge was dependent on the synthesis methodology. The particles modified by electrostatic interactions (Au-MSS/TPGS-PEI) were slightly negative (−16.9 and −5.1 mV) whereas the formulations produced by chemical linkage (Au-MSS/TPGS/PEI) resulted in positively charged nanoparticles (30.9 and 6.8 mV). The successful incorporation of the polymers was confirmed by Fourier Transformed Infrared spectroscopy and thermogravimetric analysis. Moreover, the Au-MSS functionalization did not affect the particles PTT capacity. However, the Au-MSS/TPGS/PEI nanorods displayed a decreased drug encapsulation efficiency. In vitro assays demonstrated the cytocompatibility of Au-MSS up to concentrations of 200 μg/mL, however the positively charged formulations only remained biocompatible until 100 and 125 μg/mL. Overall, the attained data confirm the successful modification of Au-MSS nanorods with TPGS and PEI as well as their applicability as PTT and drug delivery agents. • Optimization of gold-core silica shell nanorods functionalization. • Electrostatic or chemical linkage of TPGS and PEI. • Combination of drug delivery with photothermal therapy.

Dye Encapsulation in Fluorescent Core-Shell Silica Nanoparticles as Probed by Fluorescence Correlation Spectroscopy.

Synthetic advances in the formation of ultrasmall (<10 nm) fluorescent poly(ethylene glycol)-coated (PEGylated) core-shell silica nanoparticles (SNPs), enabling improved particle size and surface chemical property control have led to successful clinical translation of SNPs as diagnostic probes in oncology. Despite the success of such probes, details of the dye incorporation and resulting silica architecture are still poorly understood. Here, we employ afterpulse-corrected fluorescence correlation spectroscopy (FCS) to monitor fast fluorescence fluctuations (lag times <10-5 s) of the negatively charged cyanine dye Cy5 as a probe to study such details for dye encapsulation in 5 nm silica cores of PEGylated core-shell SNPs (C dots). Upon deposition of additional silica shells over the silica core we find that the amplitude of photo-induced cis-trans isomerization decreases, suggesting that the Cy5 dyes are located near or on the surface of the original SNP cores. In combination with time correlated fluorescence decay measurements we deduce radiative and non-radiative rates of the Cy5 dye in these particles. Results demonstrate that FCS is a well-suited tool to investigate aspects of the photophysics of fluorescent nanoparticles, and that conformational changes of cyanine dyes like Cy5 are excellent indicators for the local dye environment within ultrasmall SNPs.

Hierarchically Structured Nanoparticle Monolayers for the Tailored Etching of Nanoporous Silicon

Nanoporous silicon (NPSi) can be used in a wide range of applications including nanofiltration, thermoelectrics, photovoltaics, and catalysis. Metal-assisted chemical etching (MACE) is an electrochemical, solution-based NPSi fabrication process that relies on control over catalyst deposition to obtain the desired porous structure. In this paper, blade-casting is explored as a template-free, self-assembly deposition technique for MACE catalyst. Mixtures of silica (SiO2) and gold-core silica-shell nanoparticle (SiO2AuNP) catalysts are assembled by blade-casting, resulting in tunable hierarchical monolayers that, after MACE, produce >100 μm2 NPSi with ∼20 nm pores.

Development of gold-core silica shell nanospheres coated with poly-2-ethyl-oxazoline and β-cyclodextrin aimed for cancer therapy

Cancer is one of the major world public health problems and the currently available treatments are nonspecific and ineffective. This reality highlights the importance of developing novel therapeutic approaches. In this field, multifunctional nanomedicines have the potential to revolutionize the currently available treatments. These unique nanodevices can simultaneously act as therapeutic and imaging agents allowing the real-time monitoring of the nanoparticles biodistribution and the treatment outcome. Among the different nanoparticles, the gold-core silica shell (AuMSS) nanoparticles advantageous physicochemical and biological properties make them promising nanoplatforms for cancer therapy. Nevertheless, their successful application as an effective cancer nanomedicine is limited by the unfavorable pharmacokinetics and uncontrolled release of the therapeutic payloads. Herein, a new polymeric coating for AuMSS nanospheres was developed by combining different ratios (25/75, 50/50 and 75/25) of two materials, Poly-2-ethyl-2-oxazoline (PEOZ) and β-cyclodextrin (β-CD). The surface functionalization of AuMSS nanospheres led to a size increase and to the neutralization of the surface charge. On the other side, the nanoparticles biological performance was improved. The coated AuMSS nanospheres showed an increased cytocompatibility and internalization rate by the HeLa cancer cells. Overall, the obtained data confirm the successful modification of the AuMSS nanospheres with PEOZ and β-CD as well as their promising properties for being applied in cancer therapy.

Nanoporous silica nanoparticles functionalized with a fluorescent turn-on spirorhodamineamide as pH indicators.

We prepared water soluble, biocompatible fluorescent turn-on pH nanosensors and characterized their behavior as a function of changes in pH. The response relies on a halochromic reaction of a spirorhodamineamide derived from the bright and highly chemically and photo-stable rhodamine 6G, encapsulated in core/nanoporous shell silica nanoparticles. The fluorescent sensors displayed a fast response in the pH range of intracellular compartments. The encapsulation conferred solubility in aqueous environments and biocompatibility. We assessed the two main properties of the sensor, namely the useful pH range and the kinetics of the response, and compared them to those of the free probe. We found that such properties are strongly dependent on the functionalization and position in the silica matrix relative to the core/shell structure. Finally, we demonstrated the cellular uptake of the nanosensors, and their localization in lysosomes of living cells, by fluorescence confocal microscopy.

Bifunctional nickel-iminodiacetic acid-core-shell silica nanoparticles for the exclusion of high molecular weight proteins and purification of His-tagged recombinant proteins.

Herein, silica nanoparticles were synthesized and chemically modified with iminodiacetic acid (IDA) and Ni2+ ions surrounded by a bis-acrylamide polymeric shell to obtain a new core–shell immobilized metal affinity chromatography (IMAC) based material. These Ni2+–IDA-core–shell silica nanoparticles (Ni2+–IDA-CSS-NP) represent a new alternative for purification of His-tagged proteins and exclusion of high molecular weight (HMW) proteins at the same time. Nanoparticles presented a final size of 479.6 ± 6.9 nm determined by dynamic light scattering (DLS) and a surface charge of −37.2 ± 0.5 mV. Successful incorporation of the different compounds at every phase of synthesis was evidenced by ATR-FTIR analysis. Ni2+–IDA-CSS-NP were used for isolation of His-tagged spo0F (6His-spo0F) from E. coli lysate. Ni2+–IDA-CSS-NP presented a capacity of 4.16 ± 0.45 μg mg−1. Purification of 6His-spo0F with high selectivity and the effective exclusion of HMW proteins were evidenced by SDS-PAGE and validated through mass spectrometry analysis.

Theoretical study on femtosecond laser optical breakdown threshold in water mediated by aluminum nanoparticle coated with silica.

A strongly coupled finite element model of the optical breakdown during femtosecond laser pulse interaction, with different morphology of aluminum nanoparticles in water, was developed. This model provided new insight into the optical breakdown dependence on the nanoparticles' morphology and assembly. This model was used to theoretically investigate a 300 fs laser pulse interaction with uncoupled and plasmon coupled aluminum coated silica shell nanoparticles. This study revealed how the nanoparticles' one-dimensional assembly affected the optical breakdown threshold of its surrounding mediums. The optical breakdown threshold had much stronger dependence on the optical near-field enhancement than on the nanostructure's extinction cross-section. The maximum electric field that is outside of the aluminum nanoparticles, with 2 nm silica shell and 2 nm gap, was more than 4 times greater to the one inside of the aluminum nanoparticles. For dimer and trimer configuration, the calculated lattice cross-section temperatures at each breakdown threshold were below their melting point. It is suggested that water could be ionized by aluminum/silica (core/shell) nanostructure during femtosecond laser exposures without nanoparticles consumption. This model could increase understanding of the aluminum nanoparticle-mediated optical breakdown in water.

Synthesis and characterization of poly(N-isopropylacrylamide-co-acrylamide) mesoglobule core–silica shell nanoparticles

HypothesisHow to encapsulate poly(N-isopropylacrylamide) (PNIPAM) mesoglobule cores by silica shells greatly affects the resultant nanoparticle structures. Incorporation of acrylamide (AM) unit into PNIPAM in combination with 3-glycidyloxypropyltrimethoxysilane (GLYMO, as a coupling agent) effectively induces nucleation and growth of silica on PNIPAM core surfaces, where the –NH2 of acrylamide reacts with the epoxide of GLYMO while GLYMO further participates in subsequent sol-gel reaction of tetraethyl orthosilicate (TEOS), thereby leading to desirable particle morphology. ExperimentsPNIPAM-based core–silica shell nanoparticles were prepared by sol-gel reaction of TEOS and GLYMO in the presence of polymeric core particles. The major parameters investigated in a systematic fashion include acrylamide concentration and weight ratio of polymer:GLYMO:TEOS. GPC, DLS, DSC, FE-SEM, TEM, FTIR and TGA were then used to characterize polymeric cores and hybrid nanoparticles. FindingsThe particle morphology was governed primarily by the acrylamide content and the weight ratio of PNIPAM/AM:GLYMO:TEOS, and desirable hybrid nanoparticles with narrow particle size distribution were achieved. The LCST of PNIPAM-based mesoglobules increases with increasing acrylamide content. Encapsulation of PNIPAM-based mesoglobules with silica also reduces their thermo-sensitivity. This is the first report of developing a novel approach to prepare PNIPAM-based mesoglobule core–silica shell nanoparticles with controllable particle morphologies.

Magnetic Field-Assisted Direct Immersion SPME of Endogenous Aldehydes in Human Urine

Direct immersion solid-phase microextraction (DI-SPME) is an effective microsampling strategy for polar and ionic species in aqueous media. Nevertheless, the fiber coating is in direct contact with sample solution and affected by its conditions. To compensate this limitation and to improve the extraction efficiency, a magnetic fiber coating was prepared and employed for DI-SPME sampling under the enhancing effect of a magnetic field. Magnetic iron oxide core–shell silica nanoparticles were synthesized and embedded in polypyrrole using an in situ electropolymerization method along with simultaneous coating on the surface of a platinized stainless-steel fiber. It was then applied for magnetic-assisted DI-SPME (MA-DI-SPME) sampling of endogenous aldehydes in human urine. Sample solution pH, the magnetic field intensity, ionic strength and extraction time were evaluated as the important affecting variables. Limits of detection were obtained 0.01–0.1 ng mL−1; the calibration graphs were linear over the range of 0.1–10000 ng mL−1. The inter-fiber (fiber-to-fiber) reproducibility was found to be 10.7–12.5%. Matrix effect from urine samples was not observed at concentration levels of 0.2, 2, and 8 µg mL−1. The results showed that magnetic field increased the efficiency of DI-SPME method about two to four times. The developed strategy was successfully applied for the extraction and quantification of hexanal and heptanal (as the most important aldehyde biomarkers) in urine samples.

Synthesis of water dispersible boron core silica shell (B@SiO2) nanoparticles

Water dispersible boron nanoparticles have great potential as materials for boron neutron capture therapy of cancer and magnetic resonance imaging, if they are prepared on a large scale with uniform size and shape and hydrophilic modifiable surface. We report the first method to prepare spherical, monodisperse, water dispersible boron core silica shell nanoparticles (B@SiO2 NPs) suitable for aforementioned biomedical applications. In this method, 40 nm elemental boron nanoparticles, easily prepared by mechanical milling and carrying 10-undecenoic acid surface ligands, are hydrosilylated using triethoxysilane, followed by base-catalyzed hydrolysis of tetraethoxysilane, which forms a 10-nm silica shell around the boron core. This simple two-step process converts irregularly shaped hydrophobic boron particles into the spherically shaped uniform nanoparticles. The B@SiO2 NPs are dispersible in water and the silica shell surface can be modified with primary amines that allow for the attachment of a fluorophore and, potentially, of targeting moieties.

Polystyrene-Core, Silica-Shell Scintillant Nanoparticles for Low-Energy Radionuclide Quantification in Aqueous Media.

β-particle emitting radionuclides are useful molecular labels due to their abundance in biomolecules. Detection of β-emission from 3H, 35S, and 33P, important biological isotopes, is challenging due to the low energies (Emax ≤ 300 keV) and short penetration depths (≤0.6 mm) in aqueous media. The activity of biologically relevant β-emitters is usually measured in liquid scintillation cocktail (LSC), a mixture of energy-absorbing organic solvents, surfactants, and scintillant fluorophores, which places significant limitations on the ability to acquire time-resolved measurements directly in aqueous biological systems. As an alternative to LSC, we developed polystyrene-core, silica-shell nanoparticle scintillators (referred to as nanoSCINT) for quantification of low-energy β-particle emitting radionuclides directly in aqueous solutions. The polystyrene acts as an absorber for energy from emitted β-particles and can be loaded with a range of hydrophobic scintillant fluorophores, leading to photon emission at visible wavelengths. The silica shell serves as a hydrophilic shield for the polystyrene core, enabling dispersion in aqueous media and providing better compatibility with water-soluble analytes. While polymer and inorganic scintillating microparticles are commercially available, their large size and/or high density complicates effective dispersion throughout the sample volume. In this work, nanoSCINT nanoparticles were prepared and characterized. nanoSCINT responds to 3H, 35S, and 33P directly in aqueous solutions, does not exhibit a change in scintillation response between pH 3.0 and 9.5 or with 100 mM NaCl, and can be recovered and reused for activity measurements in bulk aqueous samples, demonstrating the potential for reduced production of LSC waste and reduced total waste volume during radionuclide quantification. The limits of detection for 1 mg/mL nanoSCINT are 130 nCi/mL for 3H, 8 nCi/mL for 35S, and <1 nCi/mL for 33P.

Enhanced distance-dependent fluorescence quenching using size tuneable core shell silica nanoparticles.

Silica nanoparticles (SNPs) have been used as favoured platforms for sensor, drug delivery and biological imaging applications, due to their ease of synthesis, size-control and bespoke physico-chemical properties. In this study, we have developed a protocol for the synthesis of size-tuneable SNPs, with diameters ranging from 20 nm to 500 nm, through the optimisation of experimental components required for nanoparticle synthesis. This protocol was also used to prepare fluorescent SNPs, via covalent linkages of fluorophores, to the nanoparticle matrix using 3-aminopropyltriethoxysilane (APTES). This enabled the fabrication of ratiometric, fluorescent, pH-sensitive nanosensors (75 nm diameter) composed SNPs covalently linked to two pH-sensitive fluorescent dyes Oregon Green (OG) and 5(6)-carboxyfluorescein (FAM) and a reference fluorescent dye 5-(6)-carboxytetramethylrhodamine (TAMRA), extending the dynamic range of measurement from pH 3.5 to 7.5. In addition, size-tuneable, core–shell SNPs, covalently linked to a fluorescent TAMRA core were synthesised to investigate distance-dependant fluorescence quenching between TAMRA and black hole quencher 2 (BHQ2®) using nanometre-sized silica shells as physical spacers. The results showed a significant fluorescence quenching could be observed over greater distances than that reported for the classical distance-dependent molecular fluorescence quenching techniques, e.g. the Förster (fluorescence) resonance energy transfer (FRET). The methods and protocols we have detailed in this manuscript will provide the basis for the reproducible production of size tunable SNPs, which will find broad utility in the development of sensors for biological applications.

Modular and Orthogonal Post-PEGylation Surface Modifications by Insertion Enabling Penta-Functional Ultrasmall Organic-Silica Hybrid Nanoparticles

Multifunctional nanoparticles (NPs) combining different functional components into a single NP platform are of great interest in the fields of nanobiotechnology and nanomedicine. Here, we report a versatile surface modification approach to modularly and orthogonally functionalize Cornell prime dots (C′ dots), ultrasmall sub-10 nm PEGylated fluorescent core–shell silica nanoparticles that have been translated into the clinic, with up to four types of different functional ligands on the NP surface. It enables the synthesis of penta-functional C′ dots integrating a variety of properties into a single NP, i.e., fluorescence detection, specific cell targeting, radioisotope chelating/labeling, ratiometric pH sensing, and drug delivery, while the overall NP size remains below 7 nm. This is achieved by taking advantage of the fact that the PEG layer of C′ dots is penetrable to small molecules. Amine- and/or thiol-functionalized silane molecules can be inserted between PEG chains and onto the silica surface of C′ ...

Fluorescence and Scattering Dual-Mode Multiplexed Imaging with Gold–Silver Alloy Core Silica Shell Nanoparticles

Gold–silver alloy core silica shell nanoparticles (Au/Ag@SiO2 NPs) with fully accordable photophysical properties were developed and used as contrast agent for multiplexed cell-imaging applications. Using a seed growth strategy, these nanoparticular labels can be designed to suit specific experimental needs and be clearly identified based on their distinctive combination of scattering and fluorescence colors. In this Article, the multiplexed cell-imaging capabilities of Au/Ag@SiO2 NPs are presented using four different combinations of core composition and fluorescence colors. In a proof of concept experiment, 86% of total nanoparticles were correctly identified by an optical microscope with a system offering fluorescence and darkfield detection capabilities. This multiplatform identification strategy was successfully applied for the detection of four different nanoparticular architectures in cell-imaging experiments.

Fabrication of a new gel polymer electrolyte containing core–shell silica–polyelectrolyte nanoparticles via activators regenerated by electron transfer atom transfer radical polymerization (ARGET-ATRP) for high-performance lithium–sulfur batteries

Presented herein is the fabrication of a new gel polymer electrolyte (GPE) containing core–shell nanoparticles for lithium–sulfur (Li–S) batteries. This work is to overcome drawbacks of poly (vinylidenefluoride) (PVDF)-based GPEs while simultaneously maintaining their beneficial electrochemical properties such as high ionic conductivity at ambient temperature and excellent chemical stability. Core–shell silica nanoparticles with silica as core and poly (vinylbenzenesulfonate) as shell was synthesized via activators regenerated by electron transfer atom transfer radical polymerization and incorporated into PVDF. The obtained composite displays ionic conductivity as high as 1.1 mS cm−1 at room temperature. Electrochemical experiments show that the new GPE acts as an effective electrolyte for high-performance lithium–sulfur batteries.

Magnetic Core–Shell Silica Nanoparticles with Large Radial Mesopores for siRNA Delivery

A novel type of magnetic core-shell silica nanoparticles is developed for small interfering RNA (siRNA) delivery. These nanoparticles are fabricated by coating super-paramagnetic magnetite nanocrystal clusters with radial large-pore mesoporous silica. The amine functionalized nanoparticles have small particle sizes around 150 nm, large radial mesopores of 12 nm, large surface area of 411 m(2) g(-1) , high pore volume of 1.13 cm(3) g(-1) and magnetization of 25 emu g(-1) . Thus, these nanoparticles possess both high loading capacity of siRNA (2 wt%) and strong magnetic response under an external magnetic field. An acid-liable coating composed of tannic acid can further protect the siRNA loaded in these nanoparticles. The coating also increases the dispersion stability of the siRNA-loaded carrier and can serve as a pH-responsive releasing switch. Using the magnetic silica nanoparticles with tannic acid coating as carriers, functional siRNA has been successfully delivered into the cytoplasm of human osteosarcoma cancer cells in vitro. The delivery is significantly enhanced with the aid of the external magnetic field.

Extended release of ketotifen from silica shell nanoparticle-laden hydrogel contact lenses: in vitro and in vivo evaluation.

Ketotifen an anti-allergic drug delivered via eye drops has major limitations, including poor ocular bioavailability and poor patient compliance. The objective of the research work was to fabricate ketotifen loaded microemulsion laden hydrogels and silica shell nanoparticle-laden (prepared from microemulsion using octyltrimethoxysilane) hydrogels to achieve extended ocular drug delivery. The porous silica shell membrane was synthesized at the liquid interface of microemulsion, which facilitates the prolongation of drug release duration from hydrogels. Drug encapsulated microemulsion and silica shell nanoparticles were dispersed separately in pre-monomer mixture, and fabricated to hydrogel. For comparison, hydrogel with direct drug entrapment was also fabricated. Significant loss in transmittance and physical properties was observed in hydrogels with direct drug entrapment. While, microemulsion and silica shell nanoparticle-laden hydrogels did not show significant effect on transmittance and physical properties. The in vitro drug release data showed extended release of ketotifen from hydrogels in following order: direct loading<microemulsion<silica shell nanoparticles. The results of cytotoxicity and animal study confirmed the safety of hydrogels. The in vivo pharmacokinetic study showed extended ketotifen release for more than 10 days. The results demonstrated the translational potential of silica shell nanoparticles for extended drug delivery without compromising the critical lens properties.

Development of novel robust nanobiocatalyst for detergents formulations and the other applications of alkaline protease.

Alkaline protease from alkaliphilic Bacillus sp. NPST-AK15 was immobilized onto functionalized and non-functionalized rattle-type magnetic core@mesoporous shell silica (RT-MCMSS) nanoparticles by physical adsorption and covalent attachment. However, the covalent attachment approach was superior for NPST-AK15 protease immobilization onto the activated RT-MCMSS-NH₂nanoparticles and was used for further studies. In comparison to free protease, the immobilized enzyme exhibited a shift in the optimal temperature and pH from 60 to 65 °C and pH 10.5-11.0, respectively. While free protease was completely inactivated after treatment for 1 h at 60 °C, the immobilized enzyme maintained 66.5% of its initial activity at similar conditions. The immobilized protease showed higher k cat and K m , than the soluble enzyme by about 1.3-, and 1.2-fold, respectively. In addition, the results revealed significant improvement of NPST-AK15 protease stability in variety of organic solvents, surfactants, and commercial laundry detergents, upon immobilization onto activated RT-MCMSS-NH₂nanoparticles. Importantly, the immobilized protease maintained significant catalytic efficiency for ten consecutive reaction cycles, and was separated easily from the reaction mixture using an external magnetic field. To the best of our knowledge this is the first report about protease immobilization onto rattle-type magnetic core@mesoporous shell silica nanoparticles that also defied activity-stability tradeoff. The results clearly suggest that the developed immobilized enzyme system is a promising nanobiocatalyst for various bioprocess applications requiring a protease.

Surface zwitterionicalization of poly(vinylidene fluoride) membranes from the entrapped reactive core–shell silica nanoparticles

We demonstrate the preparation and properties of poly(vinylidene fluoride) (PVDF) filtration membranes modified via surface zwitterionicalization mediated by reactive core–shell silica nanoparticles (SiO2 NPs). The organic/inorganic hybrid SiO2 NPs grafted with poly(methyl meth acrylate)-block-poly(2-dimethylaminoethyl methacrylate) copolymer (PMMA-b-PDMAEMA) shell were prepared by surface-initiated reversible addition fragmentation chain transfer (SI-RAFT) polymerization and then used as a membrane-making additive of PVDF membranes. The PDMAEMA exposed on membrane surface and pore walls were quaternized into zwitterionic poly(sulfobetaine methacrylate) (PSBMA) using 1,3-propane sultone (1,3-PS) as the quaternization agent. The membrane surface chemistry and morphology were analyzed by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM), respectively. The hydrophilicity, permeability and antifouling ability of the investigated membranes were evaluated in detail. It was found that the PSBMA chains brought highly-hydrophilic and strong fouling resistant characteristics to PVDF membranes due to the powerful hydration of zwitterionic surface. The SiO2 cores and PMMA chains in the hybrid NPs play a role of anchors for the linking of PSBMA chains to membrane surface. Compared to the traditional strategies for membrane hydrophilic modification, the developed method in this work combined the advantages of both blending and surface reaction.