Core‐Cone Structured Monodispersed Mesoporous Silica Nanoparticles with Ultra‐large Cavity for Protein Delivery

A new type of monodispersed mesoporous silica nanoparticles with a core–cone structure (MSN‐CC) has been synthesized. The large cone‐shaped pores are formed by silica lamellae closely packed encircling a spherical core, showing a structure similar to the flower dahlia. MSN‐CC has a large pore size of 45 nm and a high pore volume of 2.59 cm³ g⁻¹. MSN‐CC demonstrates a high loading capacity of large proteins and successfully delivers active β‐galactosidase into cells, showing their potential as efficient nanocarriers for the cellular delivery of proteins with large molecular weights.     

Low‐Density Lipoprotein‐Mimicking Nanoparticles for Tumor‐Targeted Theranostic Applications

This study introduces multifunctional lipid nanoparticles (LNPs), mimicking the structure and compositions of low‐density lipoproteins, for the tumor‐targeted co‐delivery of anti‐cancer drugs and superparamagnetic nanocrystals. Paclitaxel (4.7 wt%) and iron oxide nanocrystals (6.8 wt%, 11 nm in diameter) are co‐encapsulated within folate‐functionalized LNPs, which contain a cluster of nanocrystals with an overall diameter of about 170 nm and a zeta potential of about ‐40 mV. The folate‐functionalized LNPs enable the targeted detection of MCF‐7, human breast adenocarcinoma expressing folate receptors, in T₂‐weighted magnetic resonance images as well as the efficient intracellular delivery of paclitaxel. Paclitaxel‐free LNPs show no significant cytotoxicity up to 0.2 mg mL^?1, indicating the excellent biocompatibility of the LNPs for intracellular drug delivery applications. The targeted anti‐tumor activities of the LNPs in a mouse tumor model suggest that the low‐density lipoprotein‐mimetic LNPs can be an effective theranostic platform with excellent biocompatibility for the tumor‐targeted co‐delivery of various anti‐cancer agents.     

Real‐Time Label‐Free Monitoring of Nanoparticle Cell Uptake

The surface plasmon resonance technique in combination with whole cell sensing is used for the first time for real‐time label‐free monitoring of nanoparticle cell uptake. The uptake kinetics of several types of nanoparticles relevant to drug delivery applications into HeLa cells is determined. The cell uptake of the nanoparticles is confirmed by confocal microscopy. The cell uptake of silica nanoparticles and polyethylenimine–plasmid DNA polyplexes is studied as a function of temperature, and the uptake energies are determined by Arrhenius plots. The phase transition temperature of the HeLa cell membrane is detected when monitoring cell uptake of silica nanoparticles at different temperatures. The HeLa cell uptake of the mesoporous silica nanoparticles is energy‐independent at temperatures slightly higher than the phase transition temperature of the HeLa cell membrane, while the uptake of polyethylenimine–DNA polyplexes is energy‐dependent and linear as a function of temperature with an activation energy of Ea = 62 ± 7 kJ mol^?1 = 15 ± 2 kcal mol^?1. The HeLa cell uptake of red blood cell derived extracellular vesicles is also studied as a function of the extracellular vesicle concentration. The results show a concentration dependent behavior reaching a saturation level of the extracellular vesicle uptake by HeLa cells.     

Energy Transfer in Ionic‐Liquid‐Functionalized Inorganic Nanorods for Highly Efficient Photocatalytic Applications

Energy transfer in self‐assembled ionic liquids (ILs) and iron oxyhydroxide nanocrystals and the controlled surface chemistry of functionalized nanomaterials for photocatalytic applications are reported. Self‐assembled ILs play the role of multifunctional materials in terms of constructing a well‐designed nanostructure, controlling the surface chemistry, and triggering the energy transfer of functionalized materials. IL‐functionalized β‐FeOOH nanorods show ≈10‐fold higher performances than those of commercial materials due to the synergistic effect of well‐defined nanomaterials in diffusion‐controlled reactions, specific interactions with target pollutants, and energy transfers in hybrid materials. In particular, the energy transfer in C₄MimCl‐functionalized β‐FeOOH nanorods enhances photocatalytic activity due to the generation of Fe²⁺. The strategy described herein provides new insight into the rational design of functionalized inorganic nanomaterials for applications in emerging technologies.     

A Magnetic‐Field Guided Interface Coassembly Approach to Magnetic Mesoporous Silica Nanochains for Osteoclast‐Targeted Inhibition and Heterogeneous Nanocatalysis

1D core–shell magnetic materials with mesopores in shell are highly desired for biocatalysis, magnetic bioseparation, and bioenrichment and biosensing because of their unique microstructure and morphology. In this study, 1D magnetic mesoporous silica nanochains (Fe₃O₄@nSiO₂@mSiO₂ nanochain, Magn‐MSNCs named as FDUcs‐17C) are facilely synthesized via a novel magnetic‐field‐guided interface coassembly approach in two steps. Fe₃O₄ particles are coated with nonporous silica in a magnetic field to form 1D Fe₃O₄@nSiO₂ nanochains. A further interface coassembly of cetyltrimethylammonium bromide and silica source in water/n‐hexane biliquid system leads to 1D Magn‐MSNCs with core–shell–shell structure, uniform diameter (≈310 nm), large and perpendicular mesopores (7.3 nm), high surface area (317 m² g^?1), and high magnetization (34.9 emu g^?1). Under a rotating magnetic field, the nanochains with loaded zoledronate (a medication for treating bone diseases) in the mesopores, show an interesting suppression effect of osteoclasts differentiation, due to their 1D nanostructure that provides a shearing force in dynamic magnetic field to induce sufficient and effective reactions in cells. Moreover, by loading Au nanoparticles in the mesopores, the 1D Fe₃O₄@nSiO₂@mSiO₂‐Au nanochains can service as a catalytically active magnetic nanostirrer for hydrogenation of 4‐nitrophenol with high catalytic performance and good magnetic recyclability.     

Influence of Silicification on the Structural and Biological Properties of Buffer‐Mediated Collagen Hydrogels

A buffer‐mediated gelation route for collagen hydrogels that allows the formation of homogeneous composite and hybrid materials with various silica sources (i.e., colloidal silica and soluble silicates) at high concentration (up to 25 × 10^?3 M ) is described. Most significant improvement in rheological properties and proliferation of primary adult human dermal fibroblasts was obtained for the silicate‐based hybrid materials. A similar trend was observed in composite materials incorporating 14 nm SiO₂ nanoparticles, although to a much lesser extent, whereas larger colloids (80 and 390 nm) did not significantly impact mechanical stability and cell behavior. Modification of 80 nm particles surface with amine groups weakens the collagen‐mineral interface, resulting in the decrease of material stability and leading to particle aggregation during the course of cell proliferation experiments.     

Coating Engineering of MnFe2O4 Nanoparticles with Superhigh T2 Relaxivity and Efficient Cellular Uptake for Highly Sensitive Magnetic Resonance Imaging

Superparamagnetic nanoparticles with superhigh T₂ relaxivity and cellular uptake are strongly desired for ultrasensitive magnetic resonance imaging (MRI). Towards this end, highly monodispersed manganese ferrite nanoparticles (MNPs, 6 nm) with mPEG‐g‐PEI and PEG coatings as model system are employed in this study to investigate the coating engineering for simultaneously high T₂ relaxivity and cellular uptake. The quantitative evaluations of the intracellular uptake indicate that mPEG‐g‐PEI modified MNPs possess highly efficient cellular uptake, 2.4‐fold larger than that with mPEG coating. More significantly, this coating simultaneously leads to a remarkably high T₂ relaxivity up to 331.8 mm ⁻¹ s⁻¹, which is 4 times larger than that of the mPEG control and the largest value reported for superparamagnetic iron oxides with similar size. Modeling analysis reveals that the superior relaxivity is mainly attributed to the largely reduced diffusivity of water molecules trapped in the mPEG‐g‐PEI net. Further MRI of MDA‐MB‐231 breast cancer cells loaded MNPs with mPEG‐g‐PEI coating demonstrated the strong MR contrast in vitro effect with a T₂ relaxivity as high as 92.6 mm ⁻¹ s⁻¹, 2.5‐folds larger than reported 10 nm MNPs. This study provides a universal strategy of coating engineering of various magnetic nanoparticles for highly sensitive MRI.     

High Detectivity Solar‐Blind High‐Temperature Deep‐Ultraviolet Photodetector Based on Multi‐Layered (l00) Facet‐Oriented β‐Ga2O3 Nanobelts

Fabrication of a high‐temperature deep‐ultraviolet photodetector working in the solar‐blind spectrum range (190–280 nm) is a challenge due to the degradation in the dark current and photoresponse properties. Herein, β‐Ga₂O₃ multi‐layered nanobelts with (l00) facet‐oriented were synthesized, and were demonstrated for the first time to possess excellent mechanical, electrical properties and stability at a high temperature inside a TEM studies. As‐fabricated DUV solar‐blind photodetectors using (l00) facet‐oriented β‐Ga₂O₃ multi‐layered nanobelts demonstrated enhanced photodetective performances, that is, high sensitivity, high signal‐to‐noise ratio, high spectral selectivity, high speed, and high stability, importantly, at a temperature as high as 433 K, which are comparable to other reported semiconducting nanomaterial photodetectors. In particular, the characteristics of the photoresponsivity of the β‐Ga₂O₃ nanobelt devices include a high photoexcited current (>21 nA), an ultralow dark current (below the detection limit of 10^?14 A), a fast time response (<0.3 s), a high R_λ (≈851 A/W), and a high EQE (～4.2 × 10³). The present fabricated facet‐oriented β‐Ga₂O₃ multi‐layered nanobelt based devices will find practical applications in photodetectors or optical switches for high‐temperature environment.     

Mesoporous‐Silica‐Coated Up‐Conversion Fluorescent Nanoparticles for Photodynamic Therapy

Near‐infrared (NIR)‐to‐visible up‐conversion fluorescent nanoparticles have potential to be used for photodynamic therapy (PDT) in deep tissue because NIR light can penetrate thick tissue due to weak absorption in the optical window. Here a uniform layer of mesoporous silica is coated onto NaYF₄ up‐converting nanocrystals, with a large surface area of ≈770 m² g^?1 and an average pore size of 2 nm. A photosensitizer, zinc phthalocyanine, is incorporated into the mesoporous silica. Upon excitation by a NIR laser, the nanocrystals convert NIR light to visible light, which further activates the photosensitizer to release reactive singlet oxygen to kill cancer cells. The photosensitizer encapsulated in mesoporous silica is protected from degradation in the harsh biological environment. It is demonstrated that the photosensitizers loaded into the porous silica shell of the nanoparticles are not released out of the silica while they continuously produce singlet oxygen upon excitation by a NIR laser. The nanoparticles are reusable as the photosensitizers encapsulated in the silica are removed by soaking in ethanol.     

Molecular Modelling of Bone Morphogenetic Protein‐2 (BMP‐2) by 3D‐Rapid Prototyping

Bone morphogenetic proteins (BMP) play a decisive role in bone development and osteogenesis. In the past they have been the subject of widespread research and clinical trials as stimulants of bone growth. Recently BMP‐2 has been chemically immobilized on implant surfaces leading to enhanced bone growth and accelerated integration in sheep. Although the 3D‐structure of BMP‐2 is known the surface topography has not been the subject of a detailed analysis. Therefore we have begun implementing the technique of 3D‐rapid prototyping as a novel method for gaining topographical information on the structure‐function relationship of proteins (Laub et al., 2001, FASEB J. 15, A543). 3D‐rapid prototyping allows the construction of accurate three‐dimensional models of proteins based on their x‐ray crystallographic data. In this way we constructed a 3D scale image of BMP‐2 of the size 140 mm × 70 mm × 50 mm corresponding to a ca. 20 × 10⁶ fold magnification (scale 1 nm = 2 cm). BMP‐2 is a twisted banana‐shaped molecule consisting of a convex and a concave face and has a horn‐like protuberance cross‐turned at 180° (long axis) at each end. In the center of the convex face there is a ca. 1 nm deep crater like pit ca. 1.8 nm in diameter. The concave face is characterized by a 6–7 nm long helical groove 0.8–1.6 nm wide and ca 0.8 nm deep, into which a left‐handed helix with a pitch of 8–9 nm and a helical radius of 0.35–0.45 nm can be fitted. The concave face of BMP‐2 therefore corresponds to an imprint (groove) of a left‐handed helix i. e. to an anti‐helix or anthelix. The possible endogenous ligands and functions of these structures are unknown. These results demonstrate that full scale 3D molecular models of proteins can lead to new perceptions in understanding the interactions between ligands and proteins by macroscopic viewing and in‐hand fitting of the molecules without the aid of a computer.     

Amphiphilic Block Copolymers Directed Interface Coassembly to Construct Multifunctional Microspheres with Magnetic Core and Monolayer Mesoporous Aluminosilicate Shell

Core–shell magnetic porous microspheres have wide applications in drug delivery, catalysis and bioseparation, and so on. However, it is great challenge to controllably synthesize magnetic porous microspheres with uniform well‐aligned accessible large mesopores (>10 nm) which are highly desired for applications involving immobilization or adsorption of large guest molecules or nanoobjects. In this study, a facile and general amphiphilic block copolymer directed interfacial coassembly strategy is developed to synthesize core–shell magnetic mesoporous microspheres with a monolayer of mesoporous shell of different composition (FDUcs‐17D), such as core–shell magnetic mesoporous aluminosilicate (CS‐MMAS), silica (CS‐MMS), and zirconia‐silica (CS‐MMZS), open and large pores by employing polystyrene‐block‐poly (4‐vinylpyridine) (PS‐b‐P4VP) as an interface structure directing agent and aluminum acetylacetonate (Al(acac)₃), zirconium acetylacetonate, and tetraethyl orthosilicate as shell precursors. The obtained CS‐MMAS microspheres possess magnetic core, perpendicular mesopores (20–32 nm) in the shell, high surface area (244.7 m² g^?1), and abundant acid sites (0.44 mmol g^?1), and as a result, they exhibit superior performance in removal of organophosphorus pesticides (fenthion) with a fast adsorption dynamics and high adsorption capacity. CS‐MMAS microspheres loaded with Au nanoparticles (≈3.5 nm) behavior as a highly active heterogeneous nanocatalyst for N‐alkylation reaction for producing N‐phenylbenzylamine with a selectivity and yields of over 90% and good magnetic recyclability.     

pH‐Responsive Isoniazid‐Loaded Nanoparticles Markedly Improve Tuberculosis Treatment in Mice

Tuberculosis is a major global health problem for which improved therapeutics are needed to shorten the course of treatment and combat emergence of drug resistance. Mycobacterium tuberculosis, the etiologic agent of tuberculosis, is an intracellular pathogen of mononuclear phagocytes. As such, it is an ideal pathogen for nanotherapeutics because macrophages avidly ingest nanoparticles even without specific targeting molecules. Hence, a nanoparticle drug delivery system has the potential to target and deliver high concentrations of drug directly into M. tuberculosis‐infected cells—greatly enhancing efficacy while avoiding off‐target toxicities. Stimulus‐responsive mesoporous silica nanoparticles of two different sizes, 100 and 50 nm, are developed as carriers for the major anti‐tuberculosis drug isoniazid in a prodrug configuration. The drug is captured by the aldehyde‐functionalized nanoparticle via hydrazone bond formation and coated with poly(ethylene imine)–poly(ethylene glycol) (PEI–PEG). The drug is released from the nanoparticles in response to acidic pH at levels that naturally occur within acidified endolysosomes. It is demonstrated that isoniazid‐loaded PEI–PEG‐coated nanoparticles are avidly ingested by M. tuberculosis‐infected human macrophages and kill the intracellular bacteria in a dose‐dependent manner. It is further demonstrated in a mouse model of pulmonary tuberculosis that the nanoparticles are well tolerated and much more efficacious than an equivalent amount of free drug.     

Photoconversion‐Tunable Fluorophore Vesicles for Wavelength‐Dependent Photoinduced Cancer Therapy

Photoconversion tunability of fluorophore dye is of great interest in cancer nanomedicine such as fluorescence imaging, photodynamic therapy (PDT), and photothermal therapy (PTT). Herein, this paper reports wavelength‐dependent photoconversional polymeric vesicles of boron dipyrromethene (Bodipy) fluorophore for either PDT under 660 nm irradiation or PTT under 785 nm irradiation. After being assembled within polymeric vesicles at a high drug loading, Bodipy molecules aggregate in the conformations of both J‐type and H‐type, thereby causing red‐shifted absorption into near‐infrared region, ultralow radiative transition, and ideal resistance to photobleaching. Such vesicles further possess enhanced blood circulation, preferable tumor accumulation, as well as superior cell uptake as compared to free Bodipy. In particular, the vesicles mainly generate abundant intracellular singlet oxygen for PDT treatment under 660 nm irradiation, while they primarily produce a potent hyperthermia for PTT with tumor ablation through singlet oxygen‐synergized photothermal necrosis under 785 nm irradiation. This approach provides a facile and general strategy to tune photoconversion characteristics of fluorophore dyes for wavelength‐dependent photoinduced cancer therapy.     

Photosensitizer‐Incorporated Quadruplex DNA‐Gated Nanovechicles for Light‐Triggered,Targeted Dual Drug Delivery to Cancer Cells

A novel light‐operated vehicle for targeted intracellular drug delivery is constructed using photosensitizer‐incorporated G‐quadruplex DNA‐capped mesoporous silica nanoparticles. Upon light irradiation, the photosensitizer generates ROS, causing the DNA capping to be cleaved and allowing cargo to be released. Importantly, this platform makes it possible to develop a drug‐carrier system for the synergistic combination of chemotherapy and PDT for cancer treatment with spatial/temporal control. Furthermore, the introducing of targeting ligands further improves tumor targeting efficiency. The excellent biocompatibility, cell‐specific intracellular drug delivery, and cellular uptake properties set up the basis for future biomedical application that require in vivo controlled, targeted drug delivery.     

Novel Tunnel‐Contact‐Controlled IGZO Thin‐Film Transistors with High Tolerance to Geometrical Variability

Thin insulating layers are used to modulate a depletion region at the source of a thin‐film transistor. Bottom contact, staggered‐electrode indium gallium zinc oxide transistors with a 3 nm Al₂O₃ layer between the semiconductor and Ni source/drain contacts, show behaviors typical of source‐gated transistors (SGTs): low saturation voltage (V_{D_SAT} ≈ 3 V), change in V_{D_SAT} with a gate voltage of only 0.12 V V^?1, and flat saturated output characteristics (small dependence of drain current on drain voltage). The transistors show high tolerance to geometry: the saturated current changes only 0.15× for 2–50 µm channels and 2× for 9‐45 µm source‐gate overlaps. A higher than expected (5×) increase in drain current for a 30 K change in temperature, similar to Schottky‐contact SGTs, underlines a more complex device operation than previously theorized. Optimization for increasing intrinsic gain and reducing temperature effects is discussed. These devices complete the portfolio of contact‐controlled transistors, comprising devices with Schottky contacts, bulk barrier, or heterojunctions, and now, tunneling insulating layers. The findings should also apply to nanowire transistors, leading to new low‐power, robust design approaches as large‐scale fabrication techniques with sub‐nanometer control mature.     

Layer‐by‐Layer Nanoparticles as an Efficient siRNA Delivery Vehicle for SPARC Silencing

Efficient and safe delivery systems for siRNA therapeutics remain a challenge. Elevated secreted protein, acidic, and rich in cysteine (SPARC) protein expression is associated with tissue scarring and fibrosis. Here we investigate the feasibility of encapsulating SPARC‐siRNA in the bilayers of layer‐by‐layer (LbL) nanoparticles (NPs) with poly(L‐arginine) (ARG) and dextran (DXS) as polyelectrolytes. Cellular binding and uptake of LbL NPs as well as siRNA delivery were studied in FibroGRO cells. siGLO‐siRNA and SPARC‐siRNA were efficiently coated onto hydroxyapatite nanoparticles. The multilayered NPs were characterized with regard to particle size, zeta potential and surface morphology using dynamic light scattering and transmission electron microscopy. The SPARC‐gene silencing and mRNA levels were analyzed using ChemiDOC western blot technique and RT‐PCR. The multilayer SPARC‐siRNA incorporated nanoparticles are about 200 nm in diameter and are efficiently internalized into FibroGRO cells. Their intracellular fate was also followed by tagging with suitable reporter siRNA as well as with lysotracker dye; confocal microscopy clearly indicates endosomal escape of the particles. Significant (60%) SPARC‐gene knock down was achieved by using 0.4 pmole siRNA/μg of LbL NPs in FibroGRO cells and the relative expression of SPARC mRNA reduced significantly (60%) against untreated cells. The cytotoxicity as evaluated by xCelligence real‐time cell proliferation and MTT cell assay, indicated that the SPARC‐siRNA‐loaded LbL NPs are non‐toxic. In conclusion, the LbL NP system described provides a promising, safe and efficient delivery platform as a non‐viral vector for siRNA delivery that uses biopolymers to enhance the gene knock down efficiency for the development of siRNA therapeutics.     

Size‐Dependent Cytotoxicity of Monodisperse Silica Nanoparticles in Human Endothelial Cells

The effect that monodisperse amorphous spherical silica particles of different sizes have on the viability of endothelial cells (EAHY926 cell line) is investigated. The results indicate that exposure to silica nanoparticles causes cytotoxic damage (as indicated by lactate dehydrogenase (LDH) release) and a decrease in cell survival (as determined by the tetrazolium reduction, MTT, assay) in the EAHY926 cell line in a dose‐related manner. Concentrations leading to a 50% reduction in cell viability (TC₅₀) for the smallest particles tested (14‐, 15‐, and 16‐nm diameter) ranging from 33 to 47 µg cm^?2 of cell culture differ significantly from values assessed for the bigger nanoparticles: 89 and 254 µg cm^?2 (diameter of 19 and 60 nm, respectively). Two fine silica particles with diameters of 104 and 335 nm show very low cytotoxic response compared to nanometer‐sized particles with TC₅₀ values of 1095 and 1087 µg cm^?2, respectively. The smaller particles also appear to affect the exposed cells faster with cell death (by necrosis) being observed within just a few hours. The surface area of the tested particles is an important parameter in determining the toxicity of monodisperse amorphous silica nanoparticles.     

Colorimetric Detection of Escherichia coli Based on the Enzyme‐Induced Metallization of Gold Nanorods

A novel enzyme‐induced metallization colorimetric assay is developed to monitor and measure beta‐galactosidase (β‐gal) activity, and is further employed for colorimetric bacteriophage (phage)‐enabled detection of Escherichia coli (E. coli). This assay relies on enzymatic reaction‐induced silver deposition on the surface of gold nanorods (AuNRs). In the presence of β‐gal, the substrate p‐aminophenyl β‐d ‐galactopyranoside is hydrolyzed to produce p‐aminophenol (PAP). Reduction of silver ions by PAP generates a silver shell on the surface of AuNRs, resulting in the blue shift of the longitudinal localized surface plasmon resonance peak and multicolor changes of the detection solution from light green to orange‐red. Under optimized conditions, the detection limit for β‐gal is 128 pM, which is lower than the conventional colorimetric assay. Additionally, the assay has a broader dynamic range for β‐gal detection. The specificity of this assay for the detection of β‐gal is demonstrated against several protein competitors. Additionally, this technique is successfully applied to detect E. coli bacteria cells in combination with bacteriophage infection. Due to the simplicity and short incubation time of this enzyme‐induced metallization colorimetric method, the assay is well suited for the detection of bacteria in low‐resource settings.     

Nanoparticles of Mesoporous SO3H‐Functionalized Si‐MCM‐41 with Superior Proton Conductivity

Nanometer‐sized mesoporous silica particles of around 100‐nm diameter functionalized with a large amount of sulfonic acid groups are prepared using a simple and fast in situ co‐condensation procedure. A highly ordered hexagonal pore structure is established by applying a pre‐hydrolysis step in a high‐dilution synthesis approach, followed by adding the functionalization agent to the reaction mixture. The high‐dilution approach is advantageous for the in situ functionalization since no secondary reagents for an effective particle and framework formation are needed. Structural data are determined via electron microscopy, nitrogen adsorption, and X‐ray diffraction, proton conductivity values of the functionalized samples are measured via impedance spectroscopy. The obtained mesoporous SO₃H‐MCM‐41 nanoparticles demonstrate superior proton conductivity than their equally loaded micrometer‐sized counterparts, up to 5 × 10^?2 S cm^?1. The mesoporosity of the particles turns out to be very important for effective proton transport since non‐porous silica nanoparticles exhibit worse efficient proton transport, and the obtained particle size dependence might open up a new route in rational design of highly proton conductive materials.