ZnO nanoparticles embedded in hollow carbon fiber membrane for electrochemical H2O2 production by two-electron water oxidation reaction.

Electrochemical two-electron water oxidation reaction (2e-WOR) provides a promising alternative route for hydrogen peroxide (H2O2) production, where the design of earth abundant and environmentally friendly electrocatalysts with both high selectivity and production rate is crucial. Here we report the synthesis of ZnO nanoparticles embedded in hollow carbon fiber membrane as efficient 2e-WOR electrocatalyst by a metal-organic framework engaged electrospinning-pyrolysis method. The resultant ZnO@carbon composite fiber exhibits a foam-like hierarchical structure composed of interconnected hollow carbon nanocubes encapsulated with oxygen vacancy rich ZnO nanocrystals. Owing to the improved selectivity of ZnO, excellent conductivity of carbon fiber, promoted active site exposure and mass transfer of hollow structure, the free-standing membrane electrode shows superior 2e-WOR performances with high selectivity (83.8% at 2.8 V vs. RHE), H2O2 generation rate (19.7 µmol cm-2 min-1) and robust stability.

Silica-Based Nanoparticles for Biomedical Applications: From Nanocarriers to Biomodulators.

Silica-based nanoparticles (SNPs) are a classic type of material employed in biomedical applications because of their excellent biocompatibility and tailorable physiochemical properties. Typically, SNPs are designed as nanocarriers for therapeutics delivery, which can address a number of intrinsic drawbacks of therapeutics, including limited bioavailability, short circulation lifetime, and unfavorable biodistribution. To improve the delivery efficiency and spatiotemporal precision, tremendous efforts have been devoted to engineering the physiochemical properties of SNPs, including particle size, morphology, and mesostructure, as well as conjugating targeting ligands and/or "gatekeepers" to endow improved cell selectivity and on demand release profiles. Despite significant progress, the biologically inert nature of the bare silica framework has largely restricted the functionalities of SNPs, rendering conventional SNPs mainly as nanocarriers for targeted delivery and controlled release. To meet the requirements of next generation nanomedicines with improved efficacy and precision, new insights on the relationship between the physiochemical properties of SNPs and their biological behavior are highly valuable. Meanwhile, a conceptual shift from a simple spatiotemporal control mechanism to a more sophisticated biochemistry and signaling pathway modulation would be of great importance.In this Account, an overview of our recent contribution to the field is presented, wherein SNPs with rationally designed nanostructures and nanochemistry are applied as nanocarriers (defined as "nanomaterials being used as a transport module for another substance" according to Wikipedia) and/or biomodulators (defined as "any material that modifies a biological response" according to Wiktionary). This Account encompasses two main sections. In the first section, we focus on the conventional nanocarriers concept with new insights on the design principles of the nanostructures. We present examples to demonstrate the engineering of pore geometry, surface topology, and asymmetry of nanoparticles to achieve enhanced drug, gene, and protein delivery efficiency. The contribution of surface roughness of SNPs on improving the cellular uptake efficiency, adhesion property, and DNA transfection capacity is particularly highlighted. In the second section, we discuss novel SNPs designed as biomodulators to regulate intracellular microenvironment and cell signaling, such as the oxidative stress and glutathione levels for improving the anticancer efficacy of therapeutics and mRNA transfection in specific cell lines. The interplay between the nanoparticles, biological system, and drugs is discussed. We further discuss how to engineer the composition of SNPs to modulate metal hemostasis to realize inherent anticancer activity. Two typical examples, including modulating copper signaling for tumor vasculature targeted therapy and controlling iron signaling for macrophage polarization based immunotherapy, are presented to highlight the unique advantages of SNPs as nanosized therapeutics in comparison to molecular drugs. Moreover, utilizing these two examples, we showcase the possibility of designing SNPs with intrinsic pharmaceutical activity to indirectly control tumor growth without inducing significant cytotoxicity, thus alleviating the biosafety concerns of nanomedicines. At the end of this Account, we discuss our personal perspectives on the promises, opportunities, and issues in engineered SNPs as nanocarriers as well as their transition toward biomodulators. With a major focus on the latter scenario, the current status and possible future directions are outlined.

Dendritic Mesoporous Silica Nanoparticles with Abundant Ti4+ for Phosphopeptide Enrichment from Cancer Cells with 96% Specificity.

Selective enrichment and sensitive detection of phosphopeptides are of great significance in many bioapplications. In this work, dendritic mesoporous silica nanoparticles modified with polydopamine and chelated Ti4+ (denoted DMSNs@PDA-Ti4+) were developed to improve the enrichment selectivity of phosphopeptides. The unique central-radial pore structures endowed DMSNs@PDA-Ti4+ with a high surface area (362 m2 g-1), a large pore volume (1.37 cm3 g-1), and a high amount of chelated Ti4+ (75 µg mg-1). Compared with conventional mesoporous silica-based materials with the same functionalization (denoted mSiO2@PDA-Ti4+) and commercial TiO2, DMSNs@PDA-Ti4+ showed better selectivity and a lower detection limit (0.2 fmol/µL). Moreover, 2422 unique phosphopeptides were identified from HeLa cell extracts with a high specificity (>95%) enabled by DMSNs@PDA-Ti4+, better than those in previous reports.

Asymmetric Silica Nanoparticles with Tunable Head-Tail Structures Enhance Hemocompatibility and Maturation of Immune Cells.

Asymmetric mesoporous silica nanoparticles (MSNs) with controllable head-tail structures have been successfully synthesized. The head particle type is tunable (solid or porous), and the tail has dendritic large pores. The tail length and tail coverage on head particles are adjustable. Compared to spherical silica nanoparticles with a solid structure (Stöber spheres) or large-pore symmetrical MSNs with fully covered tails, asymmetrical head-tail MSNs (HTMSNs) show superior hemocompatibility due to reduced membrane deformation of red blood cells and decreased level of reactive oxygen species. Moreover, compared to Stöber spheres, asymmetrical HTMSNs exhibit a higher level of uptake and in vitro maturation of immune cells including dendritic cells and macrophage. This study has provided a new family of nanocarriers with potential applications in vaccine development and immunotherapy.

Dual-Functional Ultrafiltration Membrane for Simultaneous Removal of Multiple Pollutants with High Performance.

Simultaneous removal of multiple pollutants from aqueous solution with less energy consumption is crucial in water purification. Here, a novel concept of dual-functional ultrafiltration (DFUF) membrane is demonstrated by entrapment of nanostructured adsorbents into the finger-like pores of ultrafiltration (UF) membrane rather than in the membrane matrix in previous reports of blend membranes, resulting in an exceptionally high active content and simultaneous removal of multiple pollutants from water due to the dual functions of rejection and adsorption. As a demonstration, hollow porous Zr(OH)x nanospheres (HPZNs) were immobilized in poly(ether sulfone) (PES) UF membranes through polydopamine coating with a high content of 68.9 wt %. The decontamination capacity of DFUF membranes toward multiple model pollutants (colloidal gold, polyethylene glycol (PEG), Pb(II)) was evaluated against a blend membrane. Compared to the blend membrane, the DFUF membranes showed 2.1-fold increase in the effective treatment volume for the treatment of Pb(II) contaminated water from 100 ppb to below 10 ppb (WHO drinking water standard). Simultaneously, the DFUF membranes effectively removed the colloidal gold and PEG below instrument detection limit, however the blend membrane only achieved 97.6% and 96.8% rejection for colloidal gold and PEG, respectively. Moreover, the DFUF membranes showed negligible leakage of nanoadsorbents during testing; and the membrane can be easily regenerated and reused. This study sheds new light on the design of high performance multifunction membranes for drinking water purification.

An interface-directed coassembly approach to synthesize uniform large-pore mesoporous silica spheres.

A facile and controllable interface-directed coassembly (IDCA) approach is developed for the first time to synthesize uniform discrete mesoporous silica particles with a large pore size (ca. 8 nm) by using 3-dimensional macroporous carbon (3DOMC) as the nanoreactor for the confined coassembly of template molecules and silica source. By controlling the amount of the precursor solution and using Pluronic templates with different compositions, we can synthesize mesoporous silica particles with diverse morphologies (spheres, hollow spheres, and hemispheres) and different mesostructure (e.g., 2-D hexagonal and 3D face centered cubic symmetry), high surface area of about 790 m(2)/g, and large pore volume (0.98 cm(3)/g). The particle size can be tunable from submicrometer to micrometer regimes by changing the macropore diameter of 3DOMC. Importantly, this synthesis concept can be extended to fabricate multifunctional mesoporous composite spheres with a magnetic core and a mesoporous silica shell, large saturated magnetization (23.5 emu/g), and high surface area (280 m(2)/g). With the use of the magnetic mesoporous silica spheres as a magnetically recyclable absorbent, a fast and efficient removal of microcystin from water is achieved, and they can be recycled for 10 times without a significant decrease of removal efficiency for microcystin.

Synthesis of multi-functional large pore mesoporous silica nanoparticles as gene carriers.

The development of functional nanocarriers that can enhance the cellular delivery of a variety of nucleic acid agents is important in many biomedical applications such as siRNA therapy. We report the synthesis of large pore mesoporous silica nanoparticles (LPMSN) loaded with iron oxide and covalently modified by polyethyleneimine (denoted PEI-Fe-LPMSN) as carriers for gene delivery. The LPMSN have a particle size of ∼200 nm and a large pore size of 11 nm. The large pore size is essential for the formation of large iron oxide nanoparticles to increase the magnetic properties and the adsorption capacity of siRNA molecules. The magnetic property facilitates the cellular uptake of nanocarriers under an external magnetic field. PEI is covalently grafted on the silica surface to enhance the nanocarriers' affinity against siRNA molecules and to improve gene silencing performance. The PEI-Fe-LPMSN delivered siRNA-PLK1 effectively into osteosarcoma cancer cells, leading to cell viability inhibition of 80%, higher compared to the 50% reduction when the same dose of siRNA was delivered by a commercial product, oligofectamine.

Surface chemistry of spiky silica nanoparticles tailors polyethyleneimine binding and intracellular DNA delivery.

Cellular delivery of DNA using silica nanoparticles has attracted great attention. Typically, polyethyleneimine (PEI) is used to form a silica/PEI composite vector. Understanding the interactions at the silica and PEI interface is important for successful DNA delivery and transfection, especially for silica with different surface functionality. Herein, we report that a higher content of hydrogen boning formed between PEI molecules and phosphonate modified silica nanoparticles could slow down the PEI dissolution from the freeze-dried solid composites into aqueous solution than the bare silica counterpart. The pronounced PEI retention ability through phosphonation of silica nanoparticles effectively improves the transfection efficiency due to the high DNA binding affinity extracellularly, effective lysosome escape and high nuclear entry of both PEI and DNA intracellularly. Our study provides a fundamental understanding on designing effective silica-PEI-based nano-vectors for DNA delivery applications.

Asymmetric Silica Nanoparticles with Tailored Spiky Coverage Derived from Silica-Polymer Cooperative Assembly for Enhanced Hemocompatibility and Gene Delivery.

Asymmetric mesoporous silica nanoparticles (AMSNs) with one side featuring a spiky nanotopography, while the other side is smooth and solid, were synthesized via an ethylenediamine (EDA)-directed silica-polymer cooperative assembly approach. By simply varying the EDA amount (x), AMSNs-x samples with adjustable spiky surface coverage were obtained. It is demonstrated that a spiky coverage higher than 50% improved the hemocompatibility of AMSN-x, possibly due to the reduced contact area of the smooth side exposed to the red blood cell (RBC) membrane. Moreover, AMSNs-175 and AMSNs-200 with high spiky coverage enhanced their plasmid DNA (pDNA) loading and binding capability, as well as cellular uptake into HEK-293T cells, thus resulting in high transfection performance. The good hemocompatibility and high performance in pDNA delivery of AMSNs-x with high spiky coverage allow them to serve as promising nonviral vectors for potential applications in gene therapies and DNA vaccines.

Biomimetic inorganic-organic hybrid nanoparticles from magnesium-substituted amorphous calcium phosphate clusters and polyacrylic acid molecules.

Amorphous calcium phosphate (ACP) has been widely found during bone and tooth biomineralization, but the meta-stability and labile nature limit further biomedical applications. The present study found that the chelation of polyacrylic acid (PAA) molecules with Ca2+ ions in Mg-ACP clusters (~2.1 ± 0.5 nm) using a biomineralization strategy produced inorganic-organic Mg-ACP/PAA hybrid nanoparticles with better thermal stability. Mg-ACP/PAA hybrid nanoparticles (~24.0 ± 4.8 nm) were pH-responsive and could be efficiently digested under weak acidic conditions (pH 5.0-5.5). The internalization of assembled Mg-ACP/PAA nanoparticles by MC3T3-E1 cells occurred through endocytosis, indicated by laser scanning confocal microscopy and cryo-soft X-ray tomography. Our results showed that cellular lipid membranes remained intact without pore formation after Mg-ACP/PAA particle penetration. The assembled Mg-ACP/PAA particles could be digested in cell lysosomes within 24 h under weak acidic conditions, thereby indicating the potential to efficiently deliver encapsulated functional molecules. Both the in vitro and in vivo results preliminarily demonstrated good biosafety of the inorganic-organic Mg-ACP/PAA hybrid nanoparticles, which may have potential for biomedical applications.

A bioinspired route to various siliceous vesicular structures.

Various siliceous nanostructures have been successfully synthesized through the co-organization of organic molecules and inorganic silica source under mild pH conditions (pH approximately 5). A biodegradable block copolymer P123 [EO20PO70EO20, EO is poly (ethylene oxide), PO is poly (propylene oxide)] is employed as a marcomolecular template and Na2SiO39H2O as a silica source. By changing the concentrations of the reactants and/or reaction temperature, siliceous multilamellar vesicles, unilamellar nano-foams and multilamellar vesicles with sponge-like walls have been obtained. Our work provides a convenient and bioinspired route to obtain siliceous nanostructured materials with adjustable and multi-level pore structures as well as rich morphologies, which is important to understand the biomineralization mechanism. Such artificial silica nanoporous materials may find potential applications in catalysis, separations, electronics, and photonics, etc.

Lyophilization enabled disentanglement of polyethylenimine on rambutan-like silica nanoparticles for enhanced plasmid DNA delivery.

Polyethylenimine (PEI) functionalization onto nanoparticles is a widely used strategy for constructing particulate vectors for gene delivery. However, how to control the conformation of PEI chains and the resultant impact on gene transfection efficiency remains largely unexplored. Herein, we report that drying methods dramatically affect the conformation of PEI chains modified on the surface of silica nanoparticles and consequently the plasmid DNA transfection performance. Specifically, lyophilization renders less entangled PEI compared to commonly used vacuum drying as evidenced by an elevated glass transition temperature. The lyophilization induced disentangled conformation is likely associated with the solid-to-gas phase transition drying mechanism, which removes the bound crystal water content and thus reduces hydrogen bonding between amines. Moreover, we find that the stretched PEI chains on the surface of rambutan-like silica nanoparticles promote their binding capacity towards plasmid DNA molecules and thereby enhanced gene delivery and transfection efficiency. Our findings have provided new understanding about amine based polymers modified on nanoparticles, and have significant implications on the design of efficient particulate vectors for gene delivery.

Glutathione-depletion mesoporous organosilica nanoparticles as a self-adjuvant and Co-delivery platform for enhanced cancer immunotherapy.

Silica based nanoparticles have emerged as a promising vaccine delivery system for cancer immunotherapy, but their bio-degradability, adjuvanticity and the resultant antitumor activity remain to be largely improved. In this study, we report biodegradable glutathione-depletion dendritic mesoporous organosilica nanoparticles (GDMON) with a tetrasulfide-incorporated framework as a novel co-delivery platform in cancer immunotherapy. Functionalized GDMON are capable of co-delivering an antigen protein (ovalbumin) and a toll-like receptor 9 (TLR9) agonist into antigen presenting cells (APCs) and inducing endosome escape. Moreover, decreasing the intracellular glutathione (GSH) level through the -S-S-/GSH redox chemistry increases the ROS generation level both in vitro and in vivo, facilitating cytotoxic T lymphocyte (CTL) proliferation and reducing tumour growth in an aggressive B16-OVA melanoma tumour model. Our results have shown the potential of GDMON as a novel self-adjuvant and co-delivery nanocarrier for cancer vaccine.

The in-vitro bioactivity of mesoporous bioactive glasses.

Ordered mesoporous bioactive glasses (MBGs) with different compositions were prepared by using nonionic block copolymer surfactants as structure-directing agents through an evaporation-induced self-assembly process. Their in-vitro bioactivities were studied in detail by electron microscopy, Fourier-transform infrared spectroscopy, and inductively coupled plasma (ICP) atomic emission spectroscopy. The ICP element analysis results were further calculated in terms of the total consumption of Ca and P, Delta[Ca]/Delta[P] ratios, and ionic activity product (IP) of hydroxyapatite. Through the above analysis, it is clear that MBGs show a different structure-bioactivity correlation compared to conventional sol-gel-derived BGs. The in vitro bioactivity of MBGs is dependent on the Si/Ca ratio in the network when the other material parameters such as the mesostructure and texture properties (pore size, pore volume) are controlled. MBG 80S15C with relatively lower calcium content exhibits the best in vitro bioactivity, in contrast to conventional sol-gel-derived BGs where usually higher calcium percentage BGs (e.g. 60S35C) show better bioactivity. Calcination temperature is another important factor that influences the in vitro bioactivity. According to our results, MBGs calcined at 973K may possess the best in vitro bioactivity. The influences of the composition and calcination temperature upon bioactivity are explained in terms of the unique structures of MBGs.

The effect of mesoporous bioglass on osteogenesis and adipogenesis of osteoporotic BMSCs.

This study evaluated the effect of mesoporous bioglass (MBG) dissolution on the differentiation of bone marrow mesenchymal stem cells (BMSCs) derived from either sham control or ovariectomized (OVX) rats. MBG was fabricated by evaporation-induced self-assembly method. Cell proliferation was tested by Cell Counting Kit-8 assay, and cytoskeletal morphology was observed by fluorescence microscopy. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) staining and activity, Alizarin Red staining, while adipogenic differentiation was assessed by Oil Red-O staining. Quantitative real-time PCR and Western blot analysis were taken to evaluate the expression of runt-related transcription factor 2 (Runx2) and proliferator-activated receptor-γ (PPARγ). We found that MBG dissolution (0, 25, 50, 100, 200 µg/mL) was nontoxic to BMSCs growth. Sham and OVX BMSCs exhibited the highest ALP activity in 50 µg/mL of MBG osteogenic dissolution, except that sham BMSCs in 100 µg/mL showed the highest ALP activity on day 14. Runx2 was significantly upregulated after 100 µg/mL of MBG stimulation in sham and OVX BMSCs for 7 and 14 days, except that 25 µg/mL showed highest upregulation effect on OVX BMSCs at day 7. PPARγ was downregulated after MBG stimulation. The protein level of Runx2 from the sham BMSCs group was significantly upregulated after lower doses (25 and 50 µg/mL) of MBG stimulation, whereas PPARγ was downregulated in the sham and OVX BMSCs group. Thus, both the osteogenic and adipogenic abilities of BMSCs were damaged under OVX condition. Moreover, lower concentration of MBG dissolution can promote osteogenesis but inhibit adipogenesis of the sham and OVX BMSCs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3004-3014, 2016.

An approach to prepare polyethylenimine functionalized silica-based spheres with small size for siRNA delivery.

A novel approach has been developed to prepare polyethylenimine functionalized hybrid silica spheres with a diameter of ∼10 nm, which show excellent delivery efficiency of siRNA into osteosarcoma cancer cells and human colon cancer cells with a significant cell inhibition comparable to commercial agents.

Nanoparticles mimicking viral surface topography for enhanced cellular delivery.

Novel silica nanoparticles mimicking virus surface topography are prepared. It is demonstrated that increases in nanoscale surface roughness promote both binding of biomolecules and cellular uptake; thus, the cellular delivery efficiency is significantly increased (scale bars 20 µm).

Poly-L-lysine functionalized large pore cubic mesostructured silica nanoparticles as biocompatible carriers for gene delivery.

Large pore mesoporous silica nanoparticles (LP-MSNs) functionalized with poly-L-lysine (PLL) were designed as a new carrier material for gene delivery applications. The synthesized LP-MSNs are 100-200 nm in diameter and are composed of cage-like pores organized in a cubic mesostructure. The size of the cavities is about 28 nm with an entrance size of 13.4 nm. Successful grafting of PLL onto the silica surface through covalent immobilization was confirmed by X-ray photoelectron spectroscopy, solid-state (13)C magic-angle spinning nuclear magnetic resonance, Fourier transformed infrared, and thermogravimetric analysis. As a result of the particle modification with PLL, a significant increase of the nanoparticle binding capacity for oligo-DNAs was observed compared to the native unmodified silica particles. Consequently, PLL-functionalized nanoparticles exhibited a strong ability to deliver oligo DNA-Cy3 (a model for siRNA) to Hela cells. Furthermore, PLL-functionalized nanoparticles were proven to be superior as gene carriers compared to amino-functionalized nanoparticles and the native nanoparticles. The system was tested to deliver functional siRNA against minibrain-related kinase and polo-like kinase 1 in osteosarcoma cancer cells. Here, the functionalized particles demonstrated great potential for efficient gene transfer into cancer cells as a decrease of the cellular viability of the osteosarcoma cancer cells was induced. Moreover, the PLL-modified silica nanoparticles also exhibit a high biocompatibility, with low cytotoxicity observed up to 100 µg/mL.