Amino-functionalized Silica Nanoparticles Research Articles

Specific buffer effects on the formation of BSA protein corona around amino-functionalized mesoporous silica nanoparticles

The effect of buffer species on biomolecules and biomolecule-nanoparticle interactions is a phenomenon that has been either neglected, or not understood. Here, we study the formation of a BSA protein corona (PC) around amino-functionalized mesoporous silica nanoparticles (MSN-NH2) in the presence of different buffers (Tris, BES, cacodylate, phosphate, and citrate) at the same pH (7.15) and different concentrations (10, 50, and 100 mM). We find that BSA adsorption is buffer specific, with the adsorbed amount of BSA being 4.4 times higher in the presence of 100 mM Tris (184 ± 3 mg/g) than for 100 mM citrate (42 ± 2 mg/g). That is a considerable difference that cannot be explained by conventional theories. The results become clearer if the interaction energies between BSA and MSN-NH2, considering the electric double layer (EEDL) and the van der Waals (EvdW) terms, are evaluated. The buffer specific PC derives from buffer specific zeta potentials that, for MSN-NH2, are positive with Tris and negative with citrate buffers. A reversed sign of zeta potentials can be obtained by considering polarizability-dependent dispersion forces acting together with electrostatics to give the buffer specific outcome. These results are relevant not only to our understanding of the formation of the PC but may also apply to other bio- and nanosystems in biological media.

Modification of amino functionalized silica nanoparticles with L-proline and furanacrylic acid as novel composites for the efficient removal of methyl orange

The present study deals with the preparation of new composites in which L-proline (LP) and furnacrylic acid (FA) have been grafted on surface of amino functionalized silica nanoparticles (AFS). At first, AFS were prepared by sol-gel approach using tetraethoxysilane (TEOS) as silica source and aminopropyltriethoxysilane (APTES) as silica modifiers. Taking the advantage of amino group on AFS surface, LP and FA were easily grafted on silica surface to obtain LP grafted silica (AFS-LP) and FA grafted silica (AFS-FA) nanocomposites by post modification approach. As prepared composites were characterized by FTIR, SEM, XRD and TGA. The evidence of LP and FA on AFS was elucidated from the FTIR bands found at 1650–1698 cm−1 related to carbonyl group CO) of amide. Additionally, peaks observed at 2965 cm−1 (C-H stretching) of propyl groups and at 1050 cm−1 (Si-O-Si) indicated that the backbone of the material is preserved as silica. The micro images of SEM depicted that the AFS are spherical in shape and have more degree of monodispersivity whereas the SEM images of composites (AFS-LP and AFS-FA) have larger particle size and less degree of monodispersivity. Likewise, XRD peaks at 2θ (∼12°) revealed the mesoporosity of silica as well as hybrid silica and further depression in this peak in case of AFS-LP and AFS-FA depicted the existence of organic moieties on silica. TGA analysis depicted three decomposition steps (high weight loss) in case of AFS-LP and AFS-FA in contrast to two decomposition steps observed in case of AFS. The higher weight loss observed in the case of hybrid composites depicted the grafting of organic molecules on AFS. The prepared composites AFS-LP and AFS-FA were deployed to investigate their adsorption capacity to remove methyl orange (MO) from aqueous media. Experiments revealed that the composites have high adsorption capacity in acidic media (pH=2) with % removal of 85.05 % for AFS-LP and 81.70 % for AFS-FA. The experimental data was evaluated for adsorption isotherms and value of correlation factor (R2) was close to unity in case of Freundlich representing that the adsorption follows Freundlich isotherm. The data was also evaluated for kinetic models and higher values of R2 as well as closeness of experimental and calculated values of Qe predicted that adsorption of MO followed pseudo-second order kinetic model.

Evaluation of the Thermal, Chemical, Mechanical, and Microbial Stability of New Nanohybrids Based on Carboxymethyl-Scleroglucan and Silica Nanoparticles for EOR Applications.

Scleroglucan (SG) is resistant to harsh reservoir conditions such as high temperature, high shear stresses, and the presence of chemical substances. However, it is susceptible to biological degradation because bacteria use SG as a source of energy and carbon. All degradation effects lead to viscosity loss of the SG solutions, affecting their performance as an enhanced oil recovery (EOR) polymer. Recent studies have shown that nanoparticles (NPs) can mitigate these degradative effects. For this reason, the EOR performance of two new nanohybrids (NH-A and NH-B) based on carboxymethyl-scleroglucan and amino-functionalized silica nanoparticles was studied. The susceptibility of these products to chemical, mechanical, and thermal degradation was evaluated following standard procedures (API RP 63), and the microbial degradation was assessed under reservoir-relevant conditions (1311 ppm and 100 °C) using a bottle test system. The results showed that the chemical reactions for the nanohybrids obtained modified the SG triple helix configuration, impacting its viscosifying power. However, the nanohybrid solutions retained their viscosity during thermal, mechanical, and chemical degradation experiments due to the formation of a tridimensional network between the nanoparticles (NPs) and the SG. Also, NH-A and NH-B solutions exhibited bacterial control because of steric hindrances caused by nanoparticle modifications to SG. This prevents extracellular glucanases from recognizing the site of catalysis, limiting free glucose availability and generating cell death due to substrate depletion. This study provides insights into the performance of these nanohybrids and promotes their application in reservoirs with harsh conditions.

Synthesis and Characterization of New Nanohybrids Based on Carboxymethyl Scleroglucan and Silica Nanoparticles.

In this study, two new nanohybrids (NH-A and NH-B) were synthesized through carbodiimide-assisted coupling. The reaction was performed between carboxymethyl-scleroglucans (CMS-A and CMS-B) with different degrees of substitution and commercial amino-functionalized silica nanoparticles using 4-(dimethylamino)-pyridine (DMAP) and N,N'-dicyclohexylcarbodiimide (DCC) as catalysts. The morphology and properties of the nanohybrids were investigated by using transmission (TEM) and scanning electron microscopy (SEM), electron-dispersive scanning (EDS), attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FT-IR), X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (XRD), inductively coupled plasma atomic emission spectroscopy (ICP-OES), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and dynamic light scattering (DLS). The nanohybrids exhibited differences in structure due to the incorporation of polyhedral oligomeric silsesquioxane (POSS) materials. The results reveal that hybrid nanomaterials exhibit similar thermal properties but differ in morphology, chemical structure, and crystallinity properties. Finally, a viscosity study was performed on the newly obtained nanohybrid materials; viscosities of nanohybrids increased significantly in comparison to the carboxymethyl-scleroglucans, with a viscosity difference of 7.2% for NH-A and up to 32.6% for NH-B.

Design of an anticancer organoruthenium complex as the guest and polydiacetylene-coated fluorogenic nanocarrier as the host: engineering nanocarrier using ene-yne conjugation for sustained guest release, enhanced anticancer activity and reduced in vivo toxicity.

Despite the enormous efforts made over the past two decades to develop metallodrugs and nanocarriers for metallodrug delivery, there are still few precise strategies that aim to optimize the design of both metallodrugs and metallodrug carriers jointly in a concerted effort. In this work, three half-sandwich ruthenium(II) complexes with pyridylimidazo[1,5-a]pyridine ligand functionalized with polycyclic aromatic moiety (Ru(nap), Ru(ant), Ru(pyr)) are evaluated as possible anticancer candidates and polydiacetylene (PDA)-coated amino-functionalized mesoporous silica nanoparticles (AMSNs) are designed as a functional nanocarrier for drug delivery. Ru(pyr) exhibits higher cytotoxicity in HT-29 colorectal cancer cells compared to other complexes and cis-platin, but it does not exhibit better cellular uptake. Ru(pyr) is found to be preferentially accumulated in plasma, mitochondria, and ER-Golgi membrane. The complex induces cell cycle arrest in the G0/G1 phase, while higher concentrations cause programmed cell death via apoptosis. Ru(pyr) influences cancer cell adhesion property and acts as an antioxidant in HT-29 cells. In order to modulate the anticancer potency of Ru(pyr), AMSNs are used to encapsulate the complex, and then diacetylene self-assembly is allowed to deposit on the surface of the nanoparticles. Subsequently, the nanoparticles undergo topopolymerization, which results in π-conjugated PDA-Ru(pyr)@AMSNs. Owing to the ene-yne polymeric skeleton in the backbone, the non-fluorescent AMSNs turn into red-emissive particles, which are exploited for cell imaging applications. The release profile analysis reveals that such a π-conjugated polymer prevents the premature release of the complex from porous silica nanoparticles with the accelerated release of the complex in an acidic medium compared to physiological conditions. The PDA gatekeepers have also been proven to enhance the cellular internalization of Ru(pyr) with slow continuous release from the nanoformulation. Zebrafish embryo toxicity analysis suggests that the PDA-coated nanocarriers could be suitable candidates for in vivo investigations.

A new sandwich-type electrochemiluminescence sensor based on HPSNs-NH2@Au NPs and AuPdPt NPs for determination of α(2,3)-sial-Gs.

A novel sandwich-type "on-off" electrochemiluminescence (ECL) biosensor for the determination of α(2,3)-sial-Gs was designed. Specifically, amino-functionalized porous silica nanoparticles (HPSNs-NH2) were first prepared and then decorated with gold nanoparticles (Au NPs) to form HPSNs-NH2@Au NP nanocomposite, which exhibited a strong ability to enhance ECL intensity with K2S2O8 as co-reactant (signal-on) and could immobilize the target-specific binding molecules of maackia amurensis lectin (MAL). Additionally, AuPdPt trimetallic nanoparticles were prepared to serve as a quenched ECL signal indicator (signal-off) with the ability of capturing the target non-specific binding molecules of 3-aminophenylboronic acid (APBA) to form a signal label. The sandwich-type ECL biosensor was constructed based on the structure of MAL-α(2,3)-sial-Gs-APBA and achieved a determination toward α(2,3)-sial-Gs with a wide linear range from 1 fg mL-1 to 10 ng mL-1 and a low detection limit of 0.5 fg mL-1. Furthermore, the proposed ECL biosensor showed satisfactory selectivity, stability, and reproducibility for α(2,3)-sial-Gs determination.

Effectiveness of Mesoporous Silica Nanoparticles Functionalized with Benzoyl Chloride in pH-Responsive Anticorrosion Polymer Coatings.

Smart polymer coatings embedding stimuli-responsive corrosion inhibitor nanocarriers are commonly exploited, in the literature, for the development of high-performance active coatings. In this work, high-surface-area amino-functionalized mesoporous silica nanoparticles (MSN-NH2) were developed with a one-step synthesis process and then functionalized with benzoyl chloride (MSN-BC) through a reaction with amino groups. MSN-BC are able to release benzoic acid (BA) in acid and alkaline conditions as a result of the hydrolysis of the pH-sensitive amide bond. MSN-BC were embedded in polymer coatings to exploit the pH-dependent release of corrosion-inhibiting BA. After an in-depth characterization of the developed functional nanoparticles and of their pH-dependent release kinetics of BA, MSN-BC were embedded in an acrylic matrix, realizing coatings for the corrosion protection of aluminum AA2024 alloys. Results demonstrate the effectiveness of the nanoparticles' porous structure for a high loading of the anticorrosive active agent BA and the long-lasting efficiency of the coating for the corrosion protection of aluminum alloys, as validated by morphological and electrochemical impedance spectroscopy (EIS) measurements. EIS experiments were carried out with up to 21 days of exposure to a corrosive environment, revealing the potentialities of the acrylic coatings embedding MSN-BC for the protection of aluminum alloys.

Vancomycin Loaded Amino-Functionalized MCM-48 Mesoporous Silica Nanoparticles as a Promising Drug Carrier in Bone Substitutes for Bacterial Infection Management.

Orthopedic infections due to biofilm formation in biomaterial-based implants have become challenging in bone tissue engineering. In the present study, in vitro antibacterial analysis of amino-functionalized MCM-48 mesoporous silica nanoparticles (AF-MSNs) loaded with vancomycin is analyzed for its potential as a drug carrier for the sustained/controlled release of vancomycin against Staphylococcus aureus. The effective incorporation of vancomycin into the inner core of AF-MSNs was observed by alternation in the absorption frequencies obtained by Fourier transform infrared spectroscopy (FTIR). Dynamic light scattering (DLS) and high resolution-transmission electron microscopy (HR-TEM) results show that all the AF-MSNs had homogeneous spherical shapes with a mean diameter of 165.2 ± 1.25nm, and there is a slight change in the hydrodynamic diameter after vancomycin loading. Furthermore, the zeta potential of all the AF-MSNs (+ 30.5 ± 0.54mV) and AF-MSN/VA (+ 33.3 ± 0.56mV) were positively charged due to effective functionalization with 3-aminopropyl triethoxysilane (APTES). Furthermore, cytotoxicity results show that the AF-MSNs have better biocompatibility than non-functionalized MSNs (p < 0.05), and results prove AF-MSNs loaded with vancomycin show better antibacterial effect against S. aureus than non-functionalized MSNs. Results confirm that bacterial membrane integrity was affected by treatment with AF-MSNs and AF-MSN/VA by staining the treated cells with FDA/PI. Field emission scanning electron microscopy (FESEM) analysis confirmed the shrinkage of bacterial cells and membrane disintegration. Furthermore, these results demonstrate that amino-functionalized MSNs loaded with vancomycin significantly increased the anti-biofilm and biofilm inhibitory effect and can be incorporated with biomaterial-based bone substitutes and bone cement to prevent orthopedic infections post-implantation.

Mesoporous Silica Nanoparticles Coated with Carboxymethyl Chitosan for 5-Fluorouracil Ocular Delivery: Characterization, In Vitro and In Vivo Studies.

This study investigates the development of topically applied non-invasive amino-functionalized silica nanoparticles (AMSN) and O-Carboxymethyl chitosan-coated AMSN (AMSN-CMC) for ocular delivery of 5-Fluorouracil (5-FU). Particle characterization was performed by the DLS technique (Zeta-Sizer), and structural morphology was examined by SEM and TEM. The drug encapsulation and loading were determined by the indirect method using HPLC. Physicochemical characterizations were performed by NMR, TGA, FTIR, and PXRD. In vitro release was conducted through a dialysis membrane in PBS (pH 7.4) using modified Vertical Franz diffusion cells. The mucoadhesion ability of the prepared nanoparticles was tested using the particle method by evaluating the change in zeta potential. The transcorneal permeabilities of 5-FU from AMNS-FU and AMSN-CMC-FU gel formulations were estimated through excised goat cornea and compared to that of 5-FU gel formulation. Eye irritation and ocular pharmacokinetic studies from gel formulations were evaluated in rabbit eyes. The optimum formulation of AMSN-CMC-FU was found to be nanoparticles with a particle size of 249.4 nm with a polydispersity of 0.429, encapsulation efficiency of 25.8 ± 5.8%, and drug loading capacity of 5.2 ± 1.2%. NMR spectra confirmed the coating of AMSN with the CMC layer. In addition, TGA, FTIR, and PXRD confirmed the drug loading inside the AMSN-CMC. Release profiles showed 100% of the drug was released from the 5-FU gel within 4 h, while AMSN-FU gel released 20.8% of the drug and AMSN-CMC-FU gel released around 55.6% after 4 h. AMSN-CMC-FU initially exhibited a 2.45-fold increase in transcorneal flux and apparent permeation of 5-FU compared to 5-FU gel, indicating a better corneal permeation. Higher bioavailability of AMSN-FU and AMSN-CMC-FU gel formulations was found compared to 5-FU gel in the ocular pharmacokinetic study with superior pharmacokinetics parameters of AMSN-CMC-FU gel. AMSN-CMC-FU showed 1.52- and 6.14-fold higher AUC0-inf in comparison to AMSN-FU and 5-FU gel, respectively. AMSN-CMC-FU gel and AMSN-FU gel were "minimally irritating" to rabbit eyes but showed minimal eye irritation potency in comparison to the 5 FU gel. Thus, the 5-FU loaded in AMSN-CMC gel could be used as a topical formulation for the treatment of ocular cancer.

Long-Term Refrigerated Storage of Beef Using an Active Edible Film Reinforced with Mesoporous Silica Nanoparticles Containing Oregano Essential Oil (Lippia graveolens Kunth).

Beef is a fundamental part of the human diet, but it is highly susceptible to microbiological and physicochemical deterioration which decrease its shelf life. This work aimed to formulate an active edible film (AEF) incorporated with amino-functionalized mesoporous silica nanoparticles (A-MSN) loaded with Mexican oregano (Lippia graveolens Kunth) essential oil (OEO) and to evaluate its effect as a coating on fresh beef quality during refrigerated storage. The AEF was based on amaranth protein isolate (API) and chitosan (CH) (4:1, w/w), to which OEO emulsified or encapsulated in A-MSN was added. The tensile strength (36.91 ± 1.37 MPa), Young's modulus (1354.80 ± 64.6 MPa), and elongation (4.71%) parameters of AEF made it comparable with synthetic films. The antimicrobial activity of AEF against E. coli O157:H7 was improved by adding 9% (w/w) encapsulated OEO, and interactions of glycerol and A-MSN with the polymeric matrix were observed by FT-IR spectroscopy. In fresh beef, after 42 days, AEF reduced the population growth (Log CFU/cm2, relative to uncoated fresh beef) of Brochothrix thermosphacta (5.5), Escherichia coli (3.5), Pseudomonas spp. (2.8), and aerobic mesophilic bacteria (6.8). After 21 days, odor acceptability of coated fresh beef was improved, thus, enlarging the shelf life of the beef and demonstrating the preservation capacity of this film.

Sequentially responsive size reduction and drug release of core-satellite nanoparticles to enhance tumor penetration and effective tumor suppression

Poor tumor accumulation remains a serious challenge for nanomedicines to achieve ideal antitumor outcomes. The different size preferences for systematic circulation, tumor retention and deep permeation have attracted great attention when designing antineoplastic nano-delivery system. Herein, we developed a nano-system which can shrink its size in tumor microenvironment to achieve better tumor retention and penetration. In this work, the cationic bovine serum albumin-protected, doxorubicin-loaded gold nanoclusters (CAuNC-DOX) and amino-functionalized mesoporous silica nanoparticles (MSN) are connected by Fe2+ and are further coated with hyaluronic acid (HA) to obtain a core-satellite MSN-Fe-CAuNC-DOX@HA nano system (MFADH). When reaching the tumor site, the HA shell, which endows the system with both good biocompatibility and preferable tumor targeting ability, was disintegrated, followed by acid-stimulated release of small-sized pharmacological unit—CAuNC-DOX for further tumor penetration. As demonstrated in both in vitro and in vivo results, MFADH showed excellent antitumor effect, providing a proof of concept for the feasibility of shrinkable nanoplatforms in tumor treatment.

Amino-functionalized mesoporous silica nanoparticles (NH2-MSiNPs) impair the embryonic development of the sea urchin Paracentrotus lividus

Nanoparticles have found use in a wide range of applications, mainly as carriers of active biomolecules. It is thus necessary to assess their toxicity for human health, as well as for the environment, on which there is still a gap of knowledge. In this work, sea urchin Paracentrotus lividus, a widely used model for embryotoxicity and spermiotoxicity, has been used to assess potential detrimental effects of amino-functionalized mesoporous silica nanoparticles (NH2-MSiNPs) on embryonic development. Specifically, gametes quality, embryogenesis morphological and timing alterations, and cellular stress markers, such as mitochondrial functionality, were assessed in presence of different concentrations of NH2-MSiNPs in filtered seawater (FSW). Furthermore, dorsal-ventral axis development and skeletogenesis were characterized by microscopy imaging and gene expression analysis. NH2-MSiNPs determined a strong reduction in the egg fertilization rate. Consequently, the presence of NH2-MSiNPs resulted detrimental in P. lividus embryonic development, with severe morphological alterations correlated with an increased embryos mortality. Finally, NH2-MSiNPs treatment was responsible for other toxic effects, such as reduced mitochondrial function and skeletogenesis alterations, according to the reduced mineralization sites in the endoskeleton formation and the related genes altered expression. Taken together, these results suggest the potential toxic effects of NH2-MSiNPs on the marine ecosystem, with consequences for the development and reproduction of its organisms. Despite their promising potential as carriers of biomolecules, it is pivotal to consider that their uncontrolled use may result harmful to the environment and, consequently, to living organisms.

A pain reflex-inspired hydrogel for refractory wound healing

Promoting refractory wound healing remains a major therapeutic challenge. Here, a pain reflex-inspired hydrogel responsive to inflammatory microenvironmental conditions was developed and used to treat chronically infected diabetic wounds. This material was produced by reacting ε-Polylysine, which exhibits antibacterial properties, with oxidized hyaluronic acid to yield a dynamic Schiff base-crosslinked hydrogel capable of undergoing triggered dissociation in response to the lower microenvironmental pH found within refractory wounds. This hydrogel exhibited intrinsic antimicrobial activity owing to the incorporation of ε-Polylysine within the hydrogel network. To imbue the hydrogel with low pH-inducible anti-inflammatory and angiogenic activity, Schiff base bonds were used to capture Deferoxamine (DFO)-loaded amino-functionalized mesoporous silica nanoparticles (MSNs-NH2@DFO) on this hydrogel skeleton. The reflexive behaviors of the hydrogel make it ideally suited to facilitating wound healing in response to excessive local inflammation. The resultant intelligent hydrogel was highly biocompatible and exhibited robust antibacterial, anti-inflammatory, and pro-angiogenic activity in vitro and in vivo, thus effectively promoting the healing of chronically infected diabetic wounds. This novel hydrogel therefore holds great promise as a tool to promote refractory wound healing.

Cost-Effective and Selective Fluorescent Chemosensor (Pyr-NH@SiO2 NPs) for Mercury Detection in Seawater.

The release of mercury into the environment has adverse effects on humans and aquatic species, even at very low concentrations. Pyrene and its derivatives have interesting fluorescence properties that can be utilized for mercury (Hg2+) ion sensing. Herein, we reported the highly selective pyrene-functionalized silica nanoparticles (Pyr-NH@SiO2 NPs) for chemosensing mercury (Hg2+) ions in a seawater sample. The Pyr-NH@SiO2 NPs were synthesized via a two-step protocol. First, a modified Stöber method was adopted to generate amino-functionalized silica nanoparticles (NH2@SiO2 NPs). Second, 1-pyrenecarboxylic acid was coupled to NH2@SiO2 NPs using a peptide coupling reaction. As-synthesized NH2@SiO2 NPs and Pyr-NH@SiO2 NPs were thoroughly investigated by 1H-NMR, FTIR, XRD, FESEM, EDS, TGA, and BET surface area analysis. The fluorescent properties were examined in deionized water under UV-light illumination. Finally, the developed Pyr-NH@SiO2 NPs were tested as a chemosensor for Hg2+ ions detection in a broad concentration range (0–50 ppm) via photoluminescence (PL) spectroscopy. The chemosensor can selectively detect Hg2+ ions in the presence of ubiquitous ions (Na+, K+, Ca2+, Mg2+, Ba2+, Ag+, and seawater samples). The quenching of fluorescence properties with Hg2+ ions (LOD: 10 ppb) indicates that Pyr-NH@SiO2 NPs can be effectively utilized as a promising chemosensor for mercury ion detection in seawater environments.

Silica-Supported Assemblage of CuII Ions with Carbon Dots for Self-Boosting and Glutathione-Induced ROS Generation

The present work introduces coordinative binding of CuII ions with both amino-functionalized silica nanoparticles (SNs) and green-emitting carbon dots (CDs) as the pregrequisite for the CuII-assisted self-assembly of the CDs at the surface of the SNs. The produced composite SNs exhibit stable in time stimuli-responsive green fluorescence derived from the CuII-assisted assemblage of CDs. The fluorescence response of the composite SNs is sensitive to the complex formation with glutathione (GSH), enabling them to detect it with the lower limit of detection of 0.15 μM. The spin-trap-facilitated electron spin resonance technique indicated that the composite SNs are capable of self-boosting generation of ROS due to CuII→CuI reduction by carbon in low oxidation states as a part of the CDs. The intensity of the ESR signals is enhanced under the heating to 38 °C. The intensity is suppressed at the GSH concentration of 0.35 mM but is enhanced at 1.0 mM of glutathione, while it is suppressed once more at the highest intracellular concentration level of GSH (10 mM). These tendencies reveal the concentrations optimal for the scavenger or reductive potential of GSH. Flow cytometry and fluorescence and confocal microscopy methods revealed efficient cell internalization of SNs-NH2-CuII-CDs comparable with that of “free” CDs.

Evaluation of colloidal properties of amino-functionalized mesoporous silica nanoparticles conjugated with the plasmid vector pEGFP-N3 and its influence on the pDNA delivery to HeLa cells

Efforts are being made to develop gene therapy delivery systems capable of substituting the viral vectors with comparable efficiency but with fewer biosafety concerns, easier production on large-scale and improved shelf-stability. Among the potential delivery systems based on inorganic nanoparticles for plasmid DNA, mesoporous silica has been gaining significance due to its combination of biocompatibility with unique structural and chemical properties. In this study, mesoporous silica nanoparticles were grafted with different alkyl-amino groups to enable the formation of conjugates with the plasmid vector pEGFP-N3. The colloidal properties, cytotoxicity and transfection efficiency of conjugates to HeLa cells were evaluated. Spherical nanoparticles with around 90 nm of diameter were synthesized and then functionalized with propylamine, (2-aminoethyl)(ethyl)propylamine and 3-(diethylenetriamine)propyl groups. Dispersions prepared in different cell culture media and the zeta potential measurements revealed that their aggregation tendency was influenced by their functionalities. Besides, the structural integrity of the functionalized nanoparticles dispersed in Dulbecco's modified Eagle's medium was affected when sterilized in autoclave. The highest efficiency on the pEGFP-N3 conjugation was obtained with 3-(diethylenetriamine)propyl groups while the highest transfection efficiency was achieved with propyl amino groups onto the surface of mesoporous silica nanoparticles. The cytotoxicity of conjugates to HeLa cells was acceptable and the transfection efficiency was low possibly due to the aggregation observed in the cell culture medium.

Systematic Analysis of Composition, Interfacial Performance and Effects of Pulmonary Surfactant Preparations on Cellular Uptake and Cytotoxicity of Aerosolized Nanomaterials

The interplay of particles with pulmonary surfactant, a lipid‐protein material pivotal for lung function, is hypothesized as a key factor that has not been routinely considered in the current in vitro models when determining the fate of inhaled nanomaterials. To explain its influence on cellular uptake and protective effects, nanoparticles are studied on two models of alveolar cells, in the absence or presence of pulmonary surfactant. Composition and interfacial performance of native human and porcine surfactants, a commercially available bovine surfactant (Alveofact), and an artificial lung lining fluid are characterized using shotgun lipidomics and biophysical approaches (i.e., Langmuir surface balances and captive bubble surfactometry). Plain and aminofunctionalized silica nanoparticles and a novel antimycobacterial nanoformulated benzothiazinone (BTZ043) are selected as examples of neutral, positively charged and therapeutically relevant nanoparticles, respectively. They are deposited onto monocultures of human alveolar epithelial and phagocytic cell lines in the presence or absence of the surfactant preparations, modeling the alveolar milieu. Only surfactant preparations with high interfacial activity and distinctive composition mitigated the toxicity of aerosolized particles, along with a tendency of aerosolized particles to aggregate. Key requirements of surfactant preparations needed when studying interactions of nanomaterials with the pulmonary air‐blood barrier in vitro are identified.

Thermo-responsive chitosan/silk fibroin/amino-functionalized mesoporous silica hydrogels with strong and elastic characteristics for bone tissue engineering

Amino-functionalized mesoporous silica nanoparticles with radially porous architecture were optimally synthesized, and they were used together with silk fibroin and chitosan to produce a type of covalently crosslinked composite hydrogel using genipin as a crosslinker. The optimally achieved composite gels were found to be thermo-responsive at physiological temperature and pH with well-defined injectability. They were also detected to have mechanically strong and elastic characteristics. In addition, these gels showed the ability to release bioactive Si ions suited to an effective dose range in approximately linear manners for a few weeks. Studies on the cell-gel constructs revealed that the composite gels well supported the growth of seeded MC3T3-E1 cells, and the deposition of matrix components. Results obtained from the detection of alkaline phosphatase activity and the matrix mineralization in the cell-gel constructs confirmed that these composite gels had certain osteogenic capacity. The obtained results suggest that these composite gels have promising potential in bone repair and regeneration.

Effective and safe delivery of GLP-1AR and FGF-21 plasmids using amino-functionalized dual-mesoporous silica nanoparticles in vitro and in vivo

Nanomaterials have attracted increased attention because of their excellent drug-carrying capacity. However, these nanomaterials are rarely used in the treatment of metabolic diseases. Liraglutide, a glucagon-like peptide-1 receptor agonist, has been widely used in the treatment of type 2 diabetes mellitus (T2DM). Furthermore, fibroblast growth factor 21 (FGF-21) has been found to improve glucose metabolism and insulin resistance (IR). To investigate whether these two molecules have synergistic effects in vivo, we developed a novel drug delivery system using amino-functionalized and embedded dual-mesoporous silica nanoparticles (N-EDMSNs) to simultaneously carry liraglutide and FGF-21, and observed their biological effects. The resultant N-EDMSNs possessed unique hierarchical porous structures consisting of open large pores (>10 nm) and small mesopores (~2.5 nm) in the silica framework, highly positively charged surfaces and good disperisity in aqueous solution. We found that N-EDMSNs had a high loading capacity for exogenous genes and low toxicity to Hepa1-6 cells. Moreover, N-EDMSNs can simultaneously carry FGF-21 plasmids and liraglutide and successfully transfect them into Hepa1-6 cells. The transfection efficiency of N-EDMSNs was higher than that of Lipofectamine 2000 in vitro. In mice experiments, N-EDMSNs/pFGF21 treatment resulted in higher FGF-21 expression in the liver than pFGF21 treatment with hydrodynamic delivery. Compared with both pFGF21 and liraglutide, N-EDMSNs/pFGF21/Lira treatment significantly reduced the food intake, body weight, and blood glucose; increased the energy expenditure and improved hepatic IR in high-fat diet (HFD)-fed mice. Our results demonstrated that the biological effects of N-EDMSNs/pFGF21/Lira complexes were better than those of pFGF21 combined with liraglutide in vivo.

Effect of tannic acid-templated mesoporous silica nanoparticles on iron-induced oxidative stress and liver toxicity in rats.

The present study sought to investigate the effects of amino-functionalized tannic acid-templated mesoporous silica nanoparticles (TA-MS-NH2 NPs) on giving rats protection against iron-induced liver toxicity. To this end, the TA-MS-NH2 NPs were characterized using field-emission scanning electron microscope (FE-SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FTIR). Moreover, 50 Wistar rats were randomly divided into one control group (group 1) and four experimental groups (groups 2- 5) (n = 10), each of which received 100 mg/kg oral normal saline and FeSO4, respectively. Then, post-exposure hepatotoxicity and oxidative stress markers were measured in two intervals, i.e., after 4 and 24 h, followed by the measurement of the acute iron toxicity. Furthermore, hepatotoxicity markers, including the alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total antioxidant capacity (TAC), were measured via Ferric Reducing Antioxidant Power (FRAP) and 2,2,1-diphenyl-1-picrylhydrazyl (DPPH) assays. Also, malondialdehyde (MDA), total thiol groups, advanced oxidation protein products (AOPP), and nitrite/nitrate (NOx) levels were measured as oxidative stress markers in the serum samples. The results indicated that oral administration of iron significantly elevated the liver enzymes and altered the level of oxidative stress markers. It was also found that treatment with TA-MS-NH2 NPs meaningfully protected against hepatotoxicity, decreased ALT, AST, ALP, and significantly improved oxidative stress markers by decreasing MDA, AOPP, and NOx levels and increasing TAC and thiol group contents, proving that TA-MS-NH2 NPs could protect rats against iron-induced acute liver toxicity through their antioxidant features.