Silica-based Nanoparticles Research Articles

Mesoporous Silica-Based Nanoparticles in Pharmaceutical Sciences: A Mini-Review

The sustained and comprehensive need in the field of materials having immense thermal, chemical, and mechanical stability lead to the evolution of mesoporous silica nanoparticles (MSNs). Due to higher surface area and ridged tuneable particular size, silica-based mesoporous (2-50nm) drug delivery system recently becomes a prime orb for loading different guest molecules such as peptides, proteins, anticancer drugs. The most common type of mesoporous nanoparticles is MCM-41 and SBA-15. MSMs has a wide range of applications in drug delivery, imaging, and catalysis. It was in the 1970’s, when the first patent was field related to MSMs, however during 1990, the full-fledged research started for MSMs. During that era, Mobil Corporation Laboratories, Japan started synthesizing of MSMs. Yet, the University of California also pioneered in MSMs synthesis, as they claimed to prepare 4.6-30 nm MSMs with a hexagonal array of pores; they further named it as SBA-15. MSMs has huge application in drug delivery system. Because of its larger surface area of the pores, the cytotoxin or drug can be filed within the pores like a Trojan Horse. Within the intercellular environment, by the endocytosis process, the small particles will be engulfed by biological cell membranes depending on what ligands attached within MSMs i.e., loaded RNA, loaded DNA, surface protein, PEG, and monoclonal antibody. Surprisingly, advanced research on MSMs concluded that cancerous cells have the tendencies to take MCM-41 than the healthy cells of the host; giving scientists a new hope that MCM-41 will one day be used commercially to treat a certain type of cancers. Modern research also shows that for the poorly water-soluble drug, SBA-15, TUD-1, HMM-33 and FSM-16 of MSMs has tremendous potential to improve in-vitro dissolution profiling i.e., upon loading of itraconazole (a poorly water-soluble drug) within SBA-15, it can able to stimulate GI fluid and facilitate transepithelial intestinal transport which ultimately results in higher drug absorption. In this mini-review, we attempted to discuss MSNs synthesis methods, morphology, preparations, mechanisms and recent research in the MSNs Drug delivery system. Thus, we concluded that more in vivo biocompatibility studies, biodistribution studies, toxicity studies, and clinical research is the fundamental prerequisite for further advancement in mesoporous silica-based nanoparticles (MSNs).

Studies on the Exposure of Gadolinium Containing Nanoparticles with Monochromatic X-rays Drive Advances in Radiation Therapy

While conventional radiation therapy uses white X-rays that consist of a mixture of X-ray waves with various energy levels, a monochromatic X-ray (monoenergetic X-ray) has a single energy level. Irradiation of high-Z elements such as gold, silver or gadolinium with a synchrotron-generated monochromatic X-rays with the energy at or higher than their K-edge energy causes a photoelectric effect that includes release of the Auger electrons that induce DNA damage—leading to cell killing. Delivery of high-Z elements into cancer cells and tumor mass can be facilitated by the use of nanoparticles. Various types of nanoparticles containing high-Z elements have been developed. A recent addition to this growing list of nanoparticles is mesoporous silica-based nanoparticles (MSNs) containing gadolinium (Gd–MSN). The ability of Gd–MSN to inhibit tumor growth was demonstrated by evaluating effects of irradiating tumor spheroids with a precisely tuned monochromatic X-ray.

Development of Core-Shell Nanoparticle Drug Delivery Systems Based on Biomimetic Mineralization.

Among various drug-delivery systems, core-shell nanoparticles have many advantages. Inspired by nature, biomimetic synthesis has emerged as a new strategy for making core-shell nanoparticles in recent years. Biomimetic mineralization is the process by which living organisms produce minerals based on biomolecule templating that leads to the formation of hierarchically structured organic-inorganic materials. In this minireview, we mainly focus on the synthesis of core-shell nanoparticle drug-delivery systems by biomimetic mineralization. We review various biomimetic mineralization methods for fabricating core-shell nanoparticles including silica-based, calcium-based and other nanoparticles, and their applications in drug delivery. We also summarize strategies for drug loading in the biomolecule-mineralized core-shell NPs. Current challenges and future directions are also discussed.

Effective adsorptive removal of Zn2+, Cu2+, and Cr3+ heavy metals from aqueous solutions using silica-based embedded with NiO and MgO nanoparticles

In this study, the adsorptive removal of Zn2+, Cu2+, and Cr3+ metal ions from aqueous solutions onto NiO–MgO silica-based nanoparticles (SBNs) has been studied. The effect of several factors such as solution pH, initial concentration, contact time, and coexisting ions on the adsorbed amounts of single Zn2+, Cu2+, and Cr3+ ions have been investigated within an array of batch mode experiments. Interestingly, the adsorption of Cr3+ at high and low concentrations was very fast, and equilibrium was achieved within 2 min compared to Cu2+ and Zn2+ which needed 30 and 60 min to reach equilibrium, respectively. The adsorption equilibrium data fitted very well with the Sips adsorption isotherm model for Cu2+ and Zn2+, and the BET model for Cr3+ ions. The maximum uptake was maintained at 7.23, 13.76, 41.36 (ions per nm2) for Zn2+, Cu2+, and Cr3+, respectively. This equals to 37.69, 69.68, 209.51 (mg adsorbate per g adsorbent), respectively, showing the promising industrial application of those SBNs. Moreover, the adsorption uptake results increase with increasing the pH in the range of 7.0–11.0 for all investigated metal ions. The thermodynamic parameters such as the changes in Gibbs free energy (ΔGo), enthalpy (ΔHo), and entropy (ΔSo) were determined. The adsorption of Zn2+, Cu2+, and Cr3+ was spontaneous, endothermic, and physical for Cu2+ and Cr3+, while exothermic and chemical for Zn2+. The regeneration and reusability studies have proven that the NiO–MgO SBNs can be employed for the adsorptive of these metals repeatedly without impacting the adsorption capacity indicating their sustainability.

Direct reprogramming of mouse fibroblasts into hepatocyte-like cells by polyethyleneimine-modified nanoparticles through epigenetic activation of hepatic transcription factors

Direct reprogramming without an intermediate pluripotent state has great therapeutic potential in regenerative medicine. Controlling lineage-specific transcription factors (TFs) expression can change cell fate and plasticity of somatic cells. However, traditional method of direct reprogramming using viral vector mediated gene delivery remains an obstacle for clinical application due to risk of tumorigenesis. Recently, nanomaterials have been reported to be more promising delivery systems to achieve this aim, but most of methods provide DNA-based reprogramming and the underlying mechanism of direct reprogramming remains poorly understood. Here, polyethyleneimine (PEI)-modified silica nanoparticles are developed as an efficient and safe protein transduction platform for delivering two key recombinant proteins of TFs for direct lineage reprogramming of mouse embryonic fibroblasts (MEFs) to functional induced hepatocyte-like cells (iHeps). Furthermore, the mechanisms involved in lineage reprogramming of MEFs into iHeps induced by mesoporous silica nanoparticle/polyethyleneimine/transcription factor (MSN/PEI/TF) nanocomplexes are elucidated. Epigenetic mechanistic investigations uncovered reinforced enrichment of activating marks (H3K4me3 and H3K9Ac) and loss of repressive marks (H3K27me3 and H3K9me3) at the promoters of hepatic TFs during direct hepatic reprogramming upon PEI-modified silica nanoparticles. Thus, this study provides proof of principle for silica-based nanoparticles as potentially viable and safe therapeutic strategies for direct reprogramming in regenerative medicine.

Preparation and characterisation of silica-based nanoparticles for cisplatin release on cancer brain cells.

In the present work, the preparation, characterisation, and efficiency of two different silica nanostructures as release vehicles of Cisplatin are reported. The 1-hexadeciltrimethyl-ammonium bromide templating agent was used to obtain mesoporous silica nanoparticles which were later loaded with Cisplatin. While sol-gel silica was very fast prepared using an excess of acetic acid during the hydrolysis-condensation reactions of tetraethylorthosilicate and at the same time the Cisplatin was added. Several physicochemical techniques including spectroscopies, electronic microscopy, X-ray diffraction, N2 adsorption-desorption were used to characterise the silica nanostructures. An in vitro Cisplatin release test was carried out using artificial cerebrospinal fluid. Finally, the toxicity of all silica nanostructures was tested using the C6 cancer cell line. The spectroscopic results showed the suitable stabilisation of Cisplatin into the two different silica nanostructures. A large surface area was obtained for the mesoporous silica nanoparticles, while low areas were obtained in the silica nanoparticles. Cisplatin was released faster from mesoporous silica channels than from inside of aggregates nanoparticles silica. Cisplatin alone, as well as, cisplatin released from both silica nanostructures exerted a toxic effect on cancer cells. In contrast, both silica structures without the drug did not exert any toxic effect.

Effect of ion doping in silica-based nanoparticles on the hemolytic and oxidative activity in contact with human erythrocytes

AimThe aim of this study was the synthesis of ion doped silica-based nanoparticles and the evaluation of their toxic effect on erythrocytes. Materials & methodsTheir synthesis was performed using the sol-gel method, by the progressive addition of calcium, magnesium and copper ions on pure silica nanoparticles. The toxicity evaluation was based on hemolysis, lipid peroxidation, ROS, H2O2 species and antioxidant enzyme production. ResultsThe addition of Mg and Cu in the SNs presented better hemocompatibility by protecting erythrocytes from oxidative stress. ConclusionIon doping with magnesium in the investigated calcium silicate system induces a protective effect in erythrocyte membrane in compare with pure silica nanoparticles.

Geothermal silica-based fluorescent nanoparticles for the visualization of latent fingerprints

The development of silica nanoparticles from the waste of geothermal power plants and their subsequent modification using a fluorescent dye, rhodamine 6G (R-6G), has been reported. The optimum specific surface area of the silica nanoparticles before modification was 289.2 m2 g–1. After modification, the intrinsic properties of the fluorescent silica nanoparticles were studied, and the results showed that they were in their amorphous phase, with a particle size of 5–10 nm. We proposed that the interaction between R-6G and the silica nanoparticle surface was due to the hydrogen bonding, using the results from the Fourier transform infrared spectroscopy. The obtained fluorescent silica nanoparticles had excellent fluorescence enhancement of 2-fold compared to R-6G in its original state. This study reports, for the first time, the synthesis of fluorescent nanoparticles from geothermal silica and its ability to visualize latent fingerprints on different smooth dry surfaces, making it an excellent candidate for fluorescent powders in forensic applications.

Mesoporous Silica Nanoparticles for the Treatment of Complex Bone Diseases: Bone Cancer, Bone Infection and Osteoporosis.

Bone diseases, such as bone cancer, bone infection and osteoporosis, constitute a major issue for modern societies as a consequence of their progressive ageing. Even though these pathologies can be currently treated in the clinic, some of those treatments present drawbacks that may lead to severe complications. For instance, chemotherapy lacks great tumor tissue selectivity, affecting healthy and diseased tissues. In addition, the inappropriate use of antimicrobials is leading to the appearance of drug-resistant bacteria and persistent biofilms, rendering current antibiotics useless. Furthermore, current antiosteoporotic treatments present many side effects as a consequence of their poor bioavailability and the need to use higher doses. In view of the existing evidence, the encapsulation and selective delivery to the diseased tissues of the different therapeutic compounds seem highly convenient. In this sense, silica-based mesoporous nanoparticles offer great loading capacity within their pores, the possibility of modifying the surface to target the particles to the malignant areas and great biocompatibility. This manuscript is intended to be a comprehensive review of the available literature on complex bone diseases treated with silica-based mesoporous nanoparticles—the further development of which and eventual translation into the clinic could bring significant benefits for our future society.

Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer.

Three different multifunctional nanosystems based on the tethering onto mesoporous silica nanoparticles (MSN) of different fragments such as an organotin-based cytotoxic compound Ph3Sn{SCH2CH2CH2Si(OMe)3} (MSN-AP-Sn), a folate fragment (MSN-AP-FA-Sn), and an enzyme-responsive peptide able to release the metallodrug only inside cancer cells (MSN-AP-FA-PEP-S-Sn), have been synthesized and fully characterized by applying physico-chemical techniques. After that, an in vitro deep determination of the therapeutic potential of the achieved multifunctional nanovectors was carried out. The results showed a high cytotoxic potential of the MSN-AP-FA-PEP-S-Sn material against triple negative breast cancer cell line (MDA-MB-231). Moreover, a dose-dependent metallodrug-related inhibitory effect on the migration mechanism of MDA-MB-231 tumor cells was shown. Subsequently, the organotin-functionalized nanosystems have been further modified with the NIR imaging agent Alexa Fluor 647 to give three different theranostic silica-based nanoplatforms, namely, MSN-AP-Sn-AX (AX-1), MSN-AP-FA-Sn-AX (AX-2), and MSN-AP-FA-PEP-S-Sn-AX (AX-3). Their in vivo potential as theranostic markers was further evaluated in a xenograft mouse model of human breast adenocarcinoma. Owing to the combination of the receptor-mediated site targeting and the specific fine-tuned release mechanism of the organotin metallodrug, the nanotheranostic drug MSN-AP-FA-PEP-S-Sn-AX (AX-3) has shown targeted diagnostic ability in combination with enhanced therapeutic activity by promoting the inhibition of tumor growth with reduced hepatic and renal toxicity upon the repeated administration of the multifunctional nanodrug.

Effect of exposure temperature on the cell membrane disruption induced by amorphous silica nanoparticles in erythrocytes, lymphocytes, and malignant melanocytes

It is of great significance to examine carefully the potentially harmful effects of silica-based nanoparticles (NPs) on human body. In the present study, we have investigated the impact of exposure temperatures (4 °C, 15 °C, 26 °C, and 37 °C) on the cell membrane disruption induced by amorphous silica NPs of different primary diameters (28, 55, 88, 156, and 461 nm) in three different types of cells (erythrocytes, Jurkat, and B16F10), where the serum-free culture media were employed for exposure of the cells to the silica NPs. The size- and dose-dependent membranolytic activity of the silica NPs in each cell type at every temperature appeared to be given by a master curve as a function of the NP surface area per suspension volume, regardless of the NP diameter. This silica-induced membranolysis was significantly enhanced by the higher-temperature exposure of each cell type to the silica NPs. Such effects of exposure temperature on the silica-induced membranolysis in non-adherent cells of RBC and Jurkat were quite similar to each other, regardless of their difference in the presence/absence of nucleus and endocytic ability, whereas that for adherent cells of B16F10 was more remarkable. The filterability of erythrocytes also was measured at different temperatures, whereby the effect of temperature on the deformability of cell membranes was estimated. A possible mechanism underlying the effect of exposure temperature on the silica-induced membranolysis was proposed.

Strategies to Regulate the Degradability of Mesoporous Silica-based Nanoparticles for Biomedical Applications

Cancer is the second major threat to human health, and more effective cancer therapy strategies are imperative. With the development of nanotechnology, mesoporous silica-based nanoparticles (MSNs) have seen unprecedented development in cancer treatment, such as drug delivery, bioimaging and biosensing. They have received extensive attention because of their easy preparation, adjustable morphology, homogeneous pore structure, high surface areas and good biocompatibility. However, cumulative toxicity for organism caused by the low degradability of MSNs heavily hinders their translation from bench to beside. Enhancing the degradability of MSNs has provided an effective solution to solve this problem. This review aims at summarizing the effective strategies utilized to regulate the degradability of MSNs during the last few years, giving a complete overview on the recent progress and remaining challenges of degradable MSNs.

Silica-based amphiphilic Janus nanofluid with improved interfacial properties for enhanced oil recovery

Silica-based amphiphilic Janus nanoparticles were synthesized for application in the field of enhanced oil recovery. The organic hydrophobic chain was grafted onto the SiO2 nanoparticles using a Pickering emulsion method. The chemical structure of the synthesized Janus nanoparticles was then characterized by TEM and FT-IR. Their interfacial properties were systematically investigated in terms of interfacial tension, contact angle and interfacial viscosity. The obtained results showed that the oil-water interfacial tension was reduced down to 2.28 mN/m when the concentration of the Janus nanoparticles is 0.05 wt%. Moreover, the Janus nanofluids could effectively alter the wettability of the rock from oil-wet to water-wet. The displacement experiments with low-permeability sandstone cores indicated that up to 15.74% increments of the oil recovery can be obtained by injecting 100 mg/L Janus nanofluids. Attributing to their hydrophilic-lipophilic balance properties, the Janus nanoparticles can quickly transport to the oil-water interface; consequently, a stable interfacial film which is beneficial to enhance oil recovery will form at the oil-water interface. Thus, the synthesized Janus nanoparticles could serve as an ideal candidate for enhanced oil recovery.

Silica/gold nanoplatform combined with a thermosensitive gel for imaging-guided interventional therapy in PDX of pancreatic cancer

Imaging-guided interventional therapy is a promising means of minimally invasive and targeted drug delivery for patients with advanced pancreatic cancer. The effectiveness of the method depends on clear imaging and complete removal of cancer cells, especially peripheral infiltration and distant metastasis, to prevent recurrence. We synthesized hollow mesoporous silica-based nanoparticles, Gem-PFH-Au star-HMS-IGF1, with gemcitabine (Gem) and perfluorohexane (PFH) encapsulated internally, gold nanostars (Au NSs) and insulin-like growth factor-1 (IGF1) modified outwardly, to enhance multimode ultrasound (US)/computed tomography (CT)/photoacoustic (PA)/thermal imaging, guide photothermal therapy, and evaluate the effect in real time. We also prepared a type of thermosensitive gel that solidified at body temperature to facilitate the controlled release of Gem and achieve a single-administration interventional therapy. A patient-derived xenograft (PDX) mouse model was established in this study. The PDX was precisely ablated by photothermal therapy under the guidance of US/CT/PA imaging, and the residual pancreatic cancer cells were completely inhibited by Gem to prevent recurrence. This strategy ingeniously simulated the approach of surgical resection and postoperative chemotherapy in clinical procedures to treat malignancy and paves the way for interventional therapy.

Co-evaluation of interaction parameters of genomic and plasmid DNA for a new chromatographic medium

Preparation of new sorbents specific to DNA has a great significance in many biomedical fields. This study reports a new sorbent with high surface area and porosity to immobilize nucleic acids having both high molecular weight like genomic DNA (gDNA) for potential use in therapy of some immune system disease and low molecular weight like plasmid DNA (pDNA) for diagnosis, gene therapy and DNA vaccination. For this aim, silica-based pore-expanded SBA-15 nanoparticles with aminopropyl-trimethoxysilane (APTMS) for decoration of Fe+3 ions (PE SBA-15-APTMS/Fe+3) were synthesized to get high surface area for high adsorption, and embedded into cryogel column for obtaining interconnected pores to avoid diffusion limitation of DNA samples because of their viscosity features. SEM, XRD, BET, and FTIR techniques were used for characterization of samples. Synthesized hybrid column showed a superior adsorption capacity of 751.5 mg/g NP for gDNA at pH 6 with an initial concentration of 2.0 mg/mL. Hybrid column presented excellent performance for pDNA when evaluated with agarose gel electrophoresis.

Sleeping Beauty Transposon-Mediated Asparaginase Gene Delivery by a Nanoparticle Platform

Transgenic genome integration using non-viral vehicles is a promising approach for gene therapy. Previous studies reported that asparagine is a key regulator of cancer cell amino acid homeostasis, anabolic metabolism and cell proliferation. The depletion of asparagine would inhibit the growth of many cancer cells. In this study, we develop a nanoparticle delivery system to permanently integrate the asparaginase gene into the genome of human lung adenocarcinoma cells. The asparaginase plasmid and the Sleeping Beauty plasmid were co-transfected using amine-functionalized mesoporous nanoparticles into the human lung adenocarcinoma cells. The intracellular asparaginase expression led to the cell cytotoxicity for PC9 and A549 cells. In addition, the combination of the chemotherapy and the asparaginase gene therapy additively enhanced the cell cytotoxicity of PC9 and A549 cells to 69% and 63%, respectively. Finally, we showed that the stable cell clones were successfully made by puromycin selection. The doxycycline-induced expression of asparaginase caused almost complete cell death of PC9 and A549 asparaginase-integrated stable cells. This work demonstrates that silica-based nanoparticles have great potential in gene delivery for therapeutic purposes.

Comparison and process optimization of PLGA, chitosan and silica nanoparticles for potential oral vaccine delivery.

Aim: The study compared performance of nanoparticles prepared from synthetic organic, natural organic and inorganic materials as vaccine delivery platforms. Materials& methods: Various formulation (concentration, polymer/silica:surfactant ratio, solvent) and process parameters (homogenization speed and time, ultrasonication) affecting functional performance characteristics of poly(lactic-co-glycolic acid) (PLGA), chitosan and silica-based nanoparticles containing bovine serum albumin were investigated. Nanoparticles were characterized using dynamic light scattering, x-ray diffraction, scanning/transmission electron microscopy, Fourier transform infrared spectroscopy and in vitro protein release. Results: Critical formulation parameters were surfactant concentration (PLGA, silica) and polymer concentration (chitosan). Optimized nanoparticles were spherical in shape with narrow size distribution and size ranges of 100-300nm (blank) and 150-400nm (protein loaded). Protein encapsulation efficiency was 26-75% and released within 48 h in a sustained manner. Conclusion: Critical formulation and process parameters affected size of PLGA, chitosan and silica nanoparticles and protein encapsulation, while silica produced the smallest and most stable nanoparticles.

Formation of functionalized silica-based nanoparticles and their application for extraction and determination of Hg (II) ion in fish samples

An isonicotinic acid hydrazide (INAH) chemically modified fumed silica, as a novel adsorbent, was designed for the preconcentration and determination of Hg (II) ions in fish samples via the solid phase extraction followed by the hydride generation atomic absorption spectrometry (HG-AAS). In this work, the efficiency of the synthesized adsorbent was investigated to determine its ability for the extraction of the Hg (II) ions from the aqueous solutions. The extraction efficiency was investigated by optimizing of different experimental conditions, such as pH, sample volume, flow rate, adsorbent dosage, and eluent type. Under the optimal conditions, a linear calibration curve for the solid phase extraction method was obtained in the range of between 0.12 and 16.5 μg L−1. The obtained detection limit and preconcentration factor were 0.018 μg L−1 and 25, respectively (RSD > 3%). The proposed optimized method was successfully applied to fish samples.

Recent advances in the synthesis and applications of anisotropic carbon and silica-based nanoparticles

Colloidal nanoparticles with anisotropic architectures have attracted a variety of interest and attention due to different physical and chemical properties compared with the isotropic counterparts, making them promising candidates in many fundamental studies and practical applications. Particularly, carbon and silica-based anisotropic nanoparticles can be one stand out by combing both intrinsic merits of carbons and silica, such as structural stability, biocompatibility, large surface area, and ease of functionalization with the anisotropic structural complexity. In this review, we aim to provide an updated summary of the research related to the anisotropic carbon and silica-based nanostructures, covering both their synthesis and applications.

Incorporation of Nitroprusside on Silica Nanoparticles—A Strategy for Safer Use of This NO Donor in Therapy

Silica-based nanoparticles have been developed as powerful platforms for drug delivery and might also prevent undesired side effects of drugs. Here, a fast method to synthesize positively charged mesoporous silica nanoparticles (ζ = 20 ± 0.5 mV, surface area = 678 m2 g-1, and 2.3 nm of porous size) was reported. This nanomaterial was employed to anchor sodium nitroprusside (SNP), a vasodilator drug with undesired cyanide release. A remarkable incorporation of 323.9 ± 7.55 μmol of SNP per gram of nanoparticle was achieved, and a series of studies of NO release were conducted, showing efficient release of NO along with major cyanide retention (ca. 64% bound to nanoparticle). Biological assays with mammalian cells showed only a slight drop in cell viability (13%) at the highest concentration (1000 μM), while SNP exhibited an LC50 of 228 μM. Moreover, pharmacological studies demonstrated similar efficacy for vasodilation and sGC-PKG-VASP pathway activation when compared to SNP alone. Altogether, this new SNP silica nanoparticle has great potential as an alternative for wider and safer use of SNP in medicine with lower cyanide toxicity.