Organically Modified Silica Nanoparticles Research Articles

Dual-functionalized ORMOSIL nanoparticles to enhance superhydrophobicity of epoxy based coatings

Organically modified silica (ORMOSIL) nanoparticles bearing fluoro-octyl and glycidoxy-propyl groups were prepared by two simple methods: i) modification of silica (SiO2) nanoparticles with the corresponding organo-silanes and ii) sol-gel process involving tetraethoxy-silane in the presence of the organo-silanes. These hydrophobic ORMOSIL particles were mixed with epoxy resin/amino-based hardener in 2-propanol medium and sprayed on the surface of carbon-steel substrate. The epoxy coating containing ORMOSIL prepared by modification of SiO2 nanoparticle presented outstanding water repellence with water contact angle (WCA) of ≈ 162° and high roll-off ability of the water droplets. Furthermore, excellent adhesion to the substrate was evidenced by sandpaper abrasion and tape peeling test. The effect of the solid content in the 2-propanol dispersion on the superhydrophobicity character was investigated. It was observed that the spray dispersion with higher solid concentration resulted in better superhydrophobicity response, mechanical durability and effective self-cleaning behavior. The hierarchical structure and roughness were identified by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The coatings presented in this work are strong candidates for large scale production due to the low-cost and simplicity of the spraying technique and the economically feasibility of the involved compounds.

The Synthesis and Reactivity of Mesoporous and Surface-Rough Vinyl-Containing ORMOSIL Nanoparticles

Silica nanoparticles synthesized solely from organosilanes naturally possess a greater number of organic functionalities than silica nanoparticles surface-modified with organosilanes. We report the synthesis of organically modified silica (ORMOSIL) nanoparticles with a mesoporous and surface-rough morphology and with a high surface area, made solely from vinyltrimethoxy silane. We chemically modified these vinyl silica nanoparticles using bromination and hydroboration, and demonstrated the high accessibility and reactivity of the vinyl groups with an ~85% conversion of the functional groups for the bromination of both particle types, a ~60% conversion of the functional groups for the hydroboration of surface-rough particles and a 90% conversion of the functional groups for the hydroboration of mesoporous particles. We determined that the mesoporous vinyl silica nanoparticles, while having a surface area that lies between the non-porous and surface-rough vinyl silica nanoparticles, provide the greatest accessibility to the vinyl groups for boronation and allow for the incorporating of up to 3.1 × 106 B atoms per particle, making the resulting materials attractive for boron neutron capture therapy.

Transparent and superhydrophobic room temperature vulcanized (RTV) polysiloxane coatings loaded with different hydrophobic silica nanoparticles with self-cleaning characteristics

Superhydrophobic coatings based on room temperature vulcanized (RTV) polysiloxane matrix loaded with organically modified silica (ORMOSIL) nanoparticles were successfully prepared using the cost-effective and scalable one-step spraying coating approach. ORMOSIL nanoparticles were prepared by sol-gel treatment at ambient conditions through the reaction between the commercial hydrophilic silica (R200) and octyl-triethoxysilane (R200.OTS), (1H,1H,2H,2H-nonafluorohexyl)-triethoxysilane (R200.NFS) and a mixture of both (R200.OTS/NFS). The functionalization of the silica was followed by Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA). Commercial hydrophobic silica particles functionalized with siloxane (R202) and octyl-silane (R805) were also used for comparison. The presence of 20 % of R202 and R200.NFS resulted in coatings with water contact angle (WCA) higher than 160°, sliding angle <5°, high transparency and an effective self-cleaning behavior. Increasing the amount of nanoparticles increased the superhydrophobic response but the translucence decreased. Coatings containing R200.OTS particles presented high translucence and high WCA, but the sliding angle was also high, which limits their use as self-cleaning material.

Poly(tetramethylene oxide)-coated silica nanoparticles incorporated into poly(4,4′-oxydiphenylene-pyromellitimide) matrix

ABSTRACTTelechelic poly(teramethylene oxide) with two isocyanate end groups (OCN-PTMO-NCO) was synthesized by the reaction of polytetrahydrofuran (Mn = 1000 g mol−1) and hexamethylene diisocyanate in 1:2 molar ratio. The resulting macrochains were then covalently grafted to the surface of silica nanoparticles (SNPs). Thus, the inorganic nanoparticles could be thoroughly coated by a thick and soft organic shell. Thermogravimetric measurements showed that up to 85 wt.% of the organically modified SNPs (OSNPs) could be formed from the organic part. Different weight ratios of OSNPs were subsequently added to a solution of 4,4′-oxydiphenylamine/pyromellitic dianhydride poly(amic acid) (PAA) in dimethylformamide. Chemical cyclodehydration of the PAA in the presence of homogeneously dispersed OSNPs resulted in poly(4,4′-oxydiphenylene-pyromellitimide) (POPI) nanocomposites, labeled by POPI/OSNP 5, POPI/OSNP 7.5, and POPI/OSNP 10. The nanocomposites obtained were fully characterized by field emission scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction. According to the diffuse reflectance UV spectroscopy, in comparison with neat POPI, the POPI/OSNP series showed an appreciable redshift in the λmax values up to 15–20 nm. Moreover, POPI/OSNP series showed significant stability toward heat at temperatures above 540°C. The endothermic phase transitions occurred by the first thermodegradation of the resulting nanocomposites could be obviously seen in the differential thermal analysis.

Preparation of ORMOSIL nanoparticles conjugated with vitamin D3analogues and their biological evaluation

Dye-doped multifunctional organically modified silica (ORMOSIL) nanoparticles were prepared within surfactant stabilized microemulsions and conjugated with several vitamin D3derivatives.

Folic acid-conjugated organically modified silica nanoparticles for enhanced targeted delivery in cancer cells and tumor in vivo.

In this work, we report the synthesis of dye-loaded and folic acid (FA)-conjugated organically modified silica (ORMOSIL) nanoparticles as targeted optical nanoprobes for in vitro and in vivo imaging. The dye-loaded ORMOSIL (ORMD) nanoparticles are synthesized by a facile aqueous phase (oil-in-water microemulsion) approach and they have an average size of 30 nm. We observed that the functionalization of FA onto the particle surface led to a strong cellular uptake of FA-conjugated ORMD nanoparticles for pancreatic cancer Miapaca-2 cells and hepatoma SMMC7721 cells with FA receptor overexpression. Such a trend is not observed for 293T cells and breast cancer MCF7 cells as these cells possess low-expression of the FA receptor. The in vivo imaging studies demonstrate that FA-ORMD nanoparticles are preferentially accumulated in tumor sites. Histological studies reveal that no-ill effects are observed in the major organs of treated mice when compared to the untreated ones. Because of the facile synthesis process, high specificity for tumor targeting and low toxicity of FA-ORMD nanoparticles, significant potential for early-cancer detection application is expected.

PEGylation of ORMOSIL nanoparticles differently modulates the in vitro toxicity toward human lung cells.

ORganically MOdified SILica (ORMOSIL) nanoparticles (NPs) appear promising carriers for the delivery of drugs to target tissues but concerns on possible cytotoxic effects exist. Here, we studied the in vitro responses to ORMOSIL NPs in different types of human lung cells to determine the effects of polyethylene glycol (PEG) coating on NP cytotoxicity. Non-PEG NPs caused a concentration-dependent decrease of viability of all types of cells, while PEG NPs induced deleterious effects and death in carcinoma alveolar type II A549 cells but not in CCD-34Lu fibroblasts and NCI-H2347 adenocarcinoma cells. Reactive oxygen species were detected in cells incubated with PEG NPs, but their deactivation by superoxide dismutase and catalase did not protect A549 cells from death, suggesting that the oxidative stress was not the main determinant of cytotoxicity. Only in A549 cells PEG NPs modulated the transcription of genes involved in inflammation, signal transduction and cell death. Transmission electron microscopy evidenced a unique intracellular localization of PEG NPs in the lamellar bodies of A549 cells, which could be the most relevant factor leading to cytotoxicity by reducing the production of surfactant proteins and by interfering with the pulmonary surfactant system.

Extra cellular pH influences uptake and photodynamic action of pyropheophorbide-a entrapped in folate receptor targeted organically modified silica nanoparticle

Photodynamic efficacy of pyropheophorbide-a (PPa) is limited due to poor aqueous solubility. In the present study, organically modified silica nanoparticles (ORMOSIL) entrapping PPa and its folate receptor targeted conjugate (FR-Np-PPa) were prepared and the effect of pH on uptake and photodynamic action of plain and FR-Np-PPa in squamous cell carcinoma (Nt-8e) cells and adenocarcinoma of breast (MCF-7) cells were studied. Nanoformulations of PPa were characterized by absorption and fluorescence spectroscopy. Dynamic light scattering was used for size measurements. The uptake of the two nanoformulations by cells incubated in media of pH 6.5 and 7.4 was studied by confocal fluorescence microscopy and spectrofluoremetrically. Phototoxicity of PPa was studied by MTT assay. In MCF-7 and Nt-8e cells, while the uptake of PPa was observed to increase with a decrease in pH of the incubation media for folate receptor targeted Np, uptake of Np-PPa was not influenced by a change in the pH of the media. Inhibition in the uptake of PPa in presence of free folic acid for cells incubated in a medium of pH 6.5 with targeted nanoparticles was higher compared to physiological pH. Consistent with uptake studies in both the cell lines phototoxicity of PPa delivered through FR-Np-PPa was higher in medium of pH 6.5 as compared to physiological pH and phototoxicity induced by NP-PPa was independent of the pH of medium. Acidic pH enhances the photodynamic efficacy of FR-targeted nanoformulated PPa.

Theranostic Anticancer Agents Based on Internally Functionalized ORMOSIL Nanoparticles

ABSTRACTWe prepared organically modified silica (ORMOSIL) nanoparticles with internal functional groups and mesoporosity, suitable for the incorporation of modalities for both MRI imaging and cancer treatment by neutron capture therapy using gadolinium-157 nuclei. These modalities were incorporated by preparing ORMOSIL nanoparticles with reactive functional groups throughout the nanoparticle body, followed by their conversion into the metal chelating moieties inside the nanoparticles.

Fluorescent AIE dots encapsulated organically modified silica (ORMOSIL) nanoparticles for two-photon cellular imaging

2,3-Bis(4-(phenyl(4-(1,2,2-triphenylvinyl)phenyl)amino)phenyl) fumaronitrile (TPE-TPA-FN or TTF), which possesses aggregation-induced emission (AIE) characteristic, is doped in organically modified silica (ORMOSIL) nanoparticles. By increasing the weight ratio of TTF to the precursor of silica nanoparticles (the quantities of the precursors were kept the same), the fluorescence intensity of nanoparticles increased correspondingly, due to the formation of larger AIE dots in the cores of ORMOSIL nanoparticles. The fluorescent and biocompatible nanoprobes were then utilized for in vitro imaging of HeLa cells. Two-photon fluorescence microscopy clearly illustrated that the nanoparticles have the capacity of nucleus permeability, as well as cytoplasm staining towards tumor cells. Our experimental results may offer a promising method for fast and bright fluorescence imaging, as well as bio-molecule/drug delivery to cell nucleus.

Fluorescent AIE dots encapsulated organically modified silica (ORMOSIL) nanoparticles for two-photon cellular imaging

2,3-Bis(4-(phenyl(4-(1,2,2-triphenylvinyl)phenyl)amino)phenyl) fumaronitrile (TPE-TPA-FN or TTF), which possesses aggregation-induced emission (AIE) characteristic, is doped in organically modified silica (ORMOSIL) nanoparticles. By increasing the weight ratio of TTF to the precursor of silica nanoparticles (the quantities of the precursors were kept the same), the fluorescence intensity of nanoparticles increased correspondingly, due to the formation of larger AIE dots in the cores of ORMOSIL nanoparticles. The fluorescent and biocompatible nanoprobes were then utilized for in vitro imaging of HeLa cells. Two-photon fluorescence microscopy clearly illustrated that the nanoparticles have the capacity of nucleus permeability, as well as cytoplasm staining towards tumor cells. Our experimental results may offer a promising method for fast and bright fluorescence imaging, as well as bio-molecule/drug delivery to cell nucleus.

Active targeting of HER2-positive breast cancer cells by Herceptin-functionalized organically modified silica nanoparticles.

Normal micelle microemulsion method was utilized for fabrication of organically modified silica (ORMOSIL) nanoparticles. The void and dye-doped nanoparticles were synthesized in nonpolar core of two different surfactants including Aerosol OT and Tween 80. The nanoparticles were characterized using transmission electron microscopy, dynamic light scattering, and zeta potential analysis. Our results revealed that the type of surfactant molecules has a dramatic impact on the size and size distribution range, surface charge, and surface functionalization of the nanoparticles. The particles fabricated using Tween 80 had very smaller size with narrow size distribution and very lower amount of zeta potential. For specific delivery of functionalized nanoparticles to breast cancer cell line SKBR3, overexpressing human epidermal growth factor receptor 2 (HER2), both dye-doped nanoparticles fabricated with Aerosol OT or Tween 80, was conjugated to Herceptin. In vitro studies using fluorescent microscopy demonstrated that the surfactant used for preparation of the nanoparticles can affect the uptake of the particles by cells. The dye-doped functionalized ORMOSIL nanoparticles prepared with Aerosol OT showed better efficiency in the process of active targeting of HER2 receptor. Herceptin-functionalized ORMOSIL nanoparticles can be used for differentiation of HER2-positive from HER2-negative breast cancer cells or specific delivery of therapeutic and diagnostic agents and also other nanoparticles such as magnetic nanoparticles and quantum dots to breast cancer cells.FigureOrmosil bioconjugation

Development of in vitro gene delivery system using ORMOSIL nanoparticle: Analysis of p53 gene expression in cultured breast cancer cell (MCF-7).

This article reports on the application of organically modified silica (ORMOSIL) nanoparticles as an efficient in vitro gene delivery system in the recent years. Based on that prime objective, the present study addresses the possible ways to reduce cancers incidence at cellular level. In this context, ORMOSIL nanoparticles had been synthesized and incubated along with pCMV–Myc (3.8 kb) plasmid vector construct carrying p53gene, and transfected into the breast cancer cell line MCF-7 cells. Western blot analysis showed that the p53 protein was significantly expressed in breast cancer cell upon transfection. The confocal and electron microscopic studies further confirmed that the nanoparticles were accumulated in the cytoplasm and the nucleus of the cancer cells transfected with p53 gene. Interesting agarose gel electrophoresis studies revealed that the nanoparticles efficiently complex with pCMV–Myc vector. The anti-cancer properties of p53 were demonstrated by assessing the cell survival and growth rate which showed a positive linear correlation in cancer cells. Whereas, the growth rate was significantly reduced in ORMOSIL/p53/pCMV–Myc transfected breast cancer cells compared to the growth rate of non-transfected cells. The results of this approach using ORMOSIL nanoparticles as a non-viral gene delivery platform have a promising future for use as effective transfection agent for therapeutic manipulation of cancer cells and targeted cancer gene therapy in vivo.

Photosensitizer encapsulated organically modified silica nanoparticles for direct two-photon photodynamic therapy and In Vivo functional imaging

Nanoparticle-assisted two-photon imaging and near infrared (NIR) imaging are two important technologies in biophotonics research. In the present paper, organically modified silica (ORMOSIL) nanoparticles encapsulated with either PpIX (protoporphyrin IX) photosensitizers or IR-820 NIR fluorophores were synthesized and optically characterized. Using the former ORMOSIL nanoparticles, we showed: (i) direct excitation of the fluorescence of PpIX through its efficient two-photon absorption in the intracellular environment of tumor cells, and (ii) cytotoxicity towards tumor cells by PpIX under two-photon irradiation. The latter ORMOSIL nanoparticles can be used as efficient NIR fluorescent contrast agents for various types in vivo animal imaging. We applied IR-820 doped ORMOSIL nanoparticles in in vivo brain imaging of mice. We also demonstrated the applications of them to sentinel lymph node (SLN) mapping of mice. Finally, we showed that the nanoprobes could target the subcutaneously xenografted tumor of a mouse for long time observations. ORMOSIL nanoparticles have great potentials for disease diagnosis and clinical therapies.

Proinflammatory Effects of Bare and PEGylated ORMOSIL-, PLGA- and SUV-NPs on Monocytes and PMNs and Their Modulation by F-MLP

We wanted to test the proinflammatory effects of vinyltriethoxysilane-based organically modified silica nanoparticles (ORMOSIL-NPs) in vitro on blood leukocytes. Cell selectivity, cytokines/chemokines and O(2) (-) production were analyzed using nonpolyethylene glycol (PEG)ylated and PEGylated ORMOSIL-NPs, poly(lactic-co-glycolic acid) (PLGA)-NPs and small unilamellar vesicles (SUV)-NPs. ORMOSIL-NPs mostly bound to monocytes while other NPs to all leukocyte types similarly. Cell capture of PEGylated-NPs decreased strongly (ORMOSIL), moderately (PLGA) and weakly (SUV). Bare ORMOSIL-NPs effectively stimulated the production of IL-1β/IL-6/TNF-α/IL-8 by monocytes and of IL-8 by polymorphonuclear leukocytes (PMNs). NP PEGylation inhibited such effects only partially. Formyl-methionine-leucine phenylalanine (f-MLP) further increased the release of cytokines/chemokines by monocytes/PMNs primed with bare and PEGylated ORMOSIL-NPs. PEGylated SUV-NPs, bare and PEGylated ORMOSIL- and PLGA-NPs sensitize PMNs and monocytes to secrete O(2) (-) upon f-MLP stimulation. ORMOSIL-NPs are preferentially captured by circulating monocytes but stimulate both monocytes and PMNs per se or by sensitizing them to another agonist (f-MLP). PEG-coating confers stealth effects but does not completely eliminate leukocyte activation. Safe nanomedical applications require the evaluation of both intrinsic and cooperative proinflammatory potential of NPs.

Organically modified silica nanoparticles as drug delivery vehicles in photodynamic therapy

To investigate the effect of hydrophobicity, charge and size of photosensitizers (PS) on their encapsulation efficiency in organically modified silica nanoparticles (ORMOSIL), a series of alkyl ether analogs of 2-(1′-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) containing varied number of carbon units, HPPH with anionic and cationic functionalities, and HPPH analogs with molecular weight ranging from ~630 to 6000 Daltons were synthesized. Our preliminary results suggest that these factors play a significant role in encapsulation of the photosensitizers and their release from ORMOSIL nanoparticles. The synthesis and characterization of PS-encapsulated ORMOSIL and a comparative study on the effect of PS size, lipophilicity and charge on encapsulation efficiency, photophysical characteristics and release kinetics are discussed.

In vitro studies of interaction of modified silica nanoparticles with different types of immunocompetent cells

Interactions between different types of immune cells and organically-modified silica nanoparticles were studied. The silica particles functionalized with amine groups were prepared by sol-gel technique. Sheep immunoglobulin labeled with fluoresceine isothiocyanate was immobilized by adsorption onto the nanoparticles. The presence of the functional groups was confirmed by infrared absorption measurements. The level of immunocompetent cells interacting with the silica nanoparticles was estimated as the amount of fluorescence-bright cells by flow cytometry method. A low level of interaction of the peripheral blood lymphocytes with the silica nanoparticles was found. On the contrary, the macrophages are actively involved in interaction with the silica nanoparticles. The influence of different size of the silica nanoparticles and incubation time on viability and functional activity of peripheral blood lymphocytes and peritoneal macrophages were investigated.

PH-responsive silica nanoparticles for controllable 1O2 generation

pH-responsive 1O2 photosensitizing systems may serve as selective photodynamic therapy (PDT)agents by targeting the acidic interstitial fluid of many kinds of tumors. In thiswork, we present a pH-responsive nanoparticle-based platform for controllable 1O2 generation, in whicha hydrophobic 1O2 photosensitizer (meso-tetraphenylporphyrin, TPP) and a pH indicator (Bromocresol Purple,BCP, or Bromothymol Blue, BTB) are simultaneously encapsulated in organically modifiedsilica nanoparticles (OSNP). In basic conditions, the pH indicator absorbs light competitivelyand thus restricts sensitizer excitation. In acidic solution, the blue shifted absorption of thepH indicator allows the efficient excitation of the sensitizer. The pH indicator serves as an‘inner filter’ to modulate effectively the excitation of the sensitizer and thus the 1O2 generation efficiency.

In Vivo Biodistribution and Clearance Studies Using Multimodal Organically Modified Silica Nanoparticles

Successful translation of the use of nanoparticles from laboratories to clinics requires exhaustive and elaborate studies involving the biodistribution, clearance, and biocompatibility of nanoparticles for in vivo biomedical applications. We report here the use of multimodal organically modified silica (ORMOSIL) nanoparticles for in vivo bioimaging, biodistribution, clearance, and toxicity studies. We have synthesized ORMOSIL nanoparticles with diameters of 20-25 nm, conjugated with near-infrared (NIR) fluorophores and radiolabeled them with (124)I, for optical and PET imaging in vivo. The biodistribution of the nontargeted nanoparticles was studied in nontumored nude mice by optical fluorescence imaging, as well by measuring the radioactivity from harvested organs. Biodistribution studies showed a greater accumulation of nanoparticles in liver, spleen, and stomach than in kidney, heart, and lungs. The clearance studies carried out over a period of 15 days indicated hepatobiliary excretion of the nanoparticles. Selected tissues were analyzed for any potential toxicity by histological analysis, which confirmed the absence of any adverse effect or any other abnormalities in the tissues. The results demonstrate that these multimodal nanoparticles have potentially ideal attributes for use as biocompatible probes for in vivo imaging.

Using Some Nanoparticles as Contrast Agents for Optical Bioimaging

The introduction of nanometric contrast agents to optical imaging is helpful for the understanding of some biological processes at the molecular level, as well as the development of diagnostic tools and therapies. Optical imaging agents such as gold nanorods (GNRs), quantum dots (QDs), and organically modified silica (ORMOSIL) nanoparticles can overcome many drawbacks of conventional agents, such as poor contrast, photobleaching, and low chemical and optical stability in biological environment. These nanoparticles can also be developed for absorbance, emission, and scattering in the near-IR region, which allows optical approaches for deep-tissue real-time imaging. The synthesis methods and optical properties of GNRs, QDs, and ORMOSIL nanoparticles are briefly introduced, and some of their applications in optical bioimaging are demonstrated. Specific targeting, “green” synthesis methods, and optical signal demodulation are also introduced.