Hyperbranched Polyglycerol‐Doped Mesoporous Silica Nanoparticles for One‐ and Two‐Photon Activated Photodynamic Therapy

Two‐photon activated photodynamic therapy (TPA‐PDT) is a recently developed technique that shows a potential for medical application. In contrast to traditional one‐photon activated PDT, TPA‐PDT can increase the treatment depth and decrease the damage to healthy tissue by using a near‐infrared two‐photon laser. However, this technique also suffers from the fact that approved photosensitive drugs have a low two‐photon absorption cross section. In this study, it is demonstrate that doped polyglycerol mesoporous silica nanoparticles can carry a photosensitizer, Rose bengal, and can be applied in one‐ and two‐photon PDT. TPA dye‐doped mesoporous silica nanoparticles have been synthesized using a surfactant‐free route, which can be considered a TPA‐PDT platform after loading normal photosensitive drugs. The doped TPA dyes in the silica nanoparticles can transfer energy to the loading drugs via an intraparticle fluorescence resonance energy transfer (FRET) mechanism. The fluorescence lifetime and confocal laser scanning microscopy (CLSM) images obtained under different conditions demonstrated a FRET effect through both one‐ and two‐photon activated modes. The results of cytotoxicity experiments proved that this TPA‐PDT system could induce cellular apoptosis under one‐ or two‐photon irradiation. This system in principle extends the application range of TPA‐PDT.     

The Active‐Core/Active‐Shell Approach: A Strategy to Enhance the Upconversion Luminescence in Lanthanide‐Doped Nanoparticles

Nanoparticles of NaGdF₄ doped with trivalent erbium (Er³⁺) and ytterbium (Yb³⁺) are prepared by a modified thermal decomposition synthesis from trifluoroacetate precursors in 1‐octadecene and oleic acid. The nanoparticles emit visible upconverted luminescence on excitation with near‐infrared light. To minimize quenching of this luminescence by surface defects and surface‐associated ligands, the nanoparticles are coated with a shell of NaGdF₄. The intensity of the upconversion luminescence is compared for nanoparticles that were coated with an undoped shell (inert shell) and similar particles coated with a Yb³⁺‐doped shell (active shell). Luminescence is also measured for nanoparticles lacking the shell (core only), and doped with Yb³⁺ at levels corresponding to the doped and undoped core/shell materials respectively. Upconversion luminescence was more intense for the core/shell materials than for the uncoated nanoparticles, and is greatest for the materials having the “active” doped shell. Increasing the Yb³⁺ concentration in the “core‐only” nanoparticles decreases the upconversion luminescence intensity. The processes responsible for the upconversion are presented and the potential advantages of “active‐core”/“active‐shell” nanoparticles are discussed.     

One‐Step Fabrication of Multifunctional Core‐Shell Fibres by Co‐Electrospinning

In the present study, multifunctional core‐shell fibre mats were designed by co‐electrospinning. These core‐shell fibre mats have three different functionalities: 1) they are magnetic, 2) they change their optical properties with the pH of the media, and 3) they are sensitive to O₂. The shell is formed by a fluorescent pH‐sensitive co‐polymer which was previously synthesised and characterized by our research group. The core is a suspension formed by magnetic nanoparticles in a solution made up by a lipophilic indicator dye (oxygen indicator; PtOEP) and, poly‐methyl methacrylate, in THF. The magnetic nanoparticles were prepared by encapsulation of magnetite within a cross‐linked polymeric matrix (MMA‐co‐EDMA). To our knowledge, this is the first time that three functionalities (magnetic properties, sensitivity to pH, and response to O₂ concentration) were successful conjugated on the same micro‐ or nano‐material via a facile one‐step process with high yield and cost effectiveness. The morphology of the well‐organized core‐shell fibres were characterized by high resolution scanning electron microcopy (HRSEM), transmission electron microcopy (TEM), and confocal laser microscopy. The luminescent properties of core‐shell fibre mats were analysed and successfully used for simultaneously monitoring pH (from 6 to 8) and O₂, showing complete reversibility, high sensitivity (i.e., K_sv = 7.07 bar^?1 for determining O₂ in aqueous media), high magnetic susceptibility, and short response times.     

Luminescent Core/Shell Nanoparticles with a Rhabdophane LnPO4‐xH2O Structure: Stabilization of Ce3+‐Doped Compositions

The core/shell strategy has been successfully developed for rhabdophane lanthanide phosphate aqueous colloids. The growth of a LaPO₄‐xH₂O shell around Ce,Tb‐doped core nanoparticles increases their stability against oxidation. A bright green luminescence is thus preserved in sol–gel films whose fabrication requires silica coating and thermal treatment of the core/shell nanoparticles.     

Fluorescence Quenching upon Binding of Copper Ions in Dye‐Doped and Ligand‐Capped Polymer Nanoparticles: A Simple Way to Probe the Dye Accessibility in Nano‐Sized Templates

The synthesis and properties of well‐defined core–shell type fluorescent metal‐chelating polymer nanoparticles NP, in the 15 nm diameter range, with a fluorophore (9,10‐diphenylanthracene: DPA) entrapped in the particle core and a selective ligand (1,4,8,11‐tetraazacyclotetradecane: Cyclam), grafted onto the surface are presented. NPs with different number of dye‐per‐particle are readily obtained by entrapment of the fluorophore within the polymer core. The ligand‐coated NPs exhibit a high affinity for Cu²⁺ ions in aqueous solution and quenching of the DPA fluorescence is observed upon binding of copper. The quenching of fluorescence arises through energy transfer (FRET) from the dye to the copper‐cyclam complexes that form at the NP surface with an operating distance (d) in the 2 nm range. A simple core–shell model accounts for the steady‐state and time‐resolved fluorescence titration experiments: dye molecules located in the outer sphere (thickness d) of the NPs are quenched while the fluorescence of dyes embedded more deeply is not affected by the binding of copper ions. The observed high quenching efficiency (60–65 %), which is tightly correlated to the volumic and microstructural features of the NPs, shed light on the enhanced accessibility inherent in nano‐sized templates. The response towards different metal ions was investigated and this confirmed the selectivity of the nanoparticle template‐assembled sensor for cupric ions.     

Controlled Release and Absorption Resonance of Fluorescent Silica‐Coated Platinum Nanoparticles

Aggregation‐driven seeded growth of uniform platinum nanoparticles and exclusive silica‐coating of the as‐grown platinum nanoparticles have been achieved successfully. Fluorescent Pt@SiO₂ nanoparticles have also been reproducibly prepared via effective co‐condensation of silanized dye molecules with tetraethylorthosilicate. The dye‐loaded Pt@SiO₂ nanoparticles have been exploited as model carriers for thermal‐responsive controlled release of guest molecules via slow hydrolysis/dissolution of silica shells; importantly, the encapsulated platinum cores have also been used as nanoprobes to simultaneously investigate their controlled release process. Meanwhile, unique size‐sensitive absorbance resonance in the dye‐loaded Pt@SiO₂ nanoparticles has been demonstrated for the first time, and it is expected to find novel application.     

Plasmon‐Enhanced Fluorescence‐Based Core–Shell Gold Nanorods as a Near‐IR Fluorescent Turn‐On Sensor for the Highly Sensitive Detection of Pyrophosphate in Aqueous Solution

Developing plasmon‐enhanced fluorescence (PEF) technology for identifying important biological molecules has a profound impact on biosensing and bioimaging. However, exploration of PEF for biological application is still at a very early stage. Herein, novel PEF‐based core–shell nanostructures as a near‐infrared fluorescent turn‐on sensor for highly sensitive and selective detection of pyrophosphate (PPi) in aqueous solution are proposed. This nanostructure gold nanorod (AuNR)@SiO₂@meso‐tetra(4‐carboxyphenyl) porphyrin (TCPP) contains a gold nanorod core with an aspect ratio of 2.3, a silica shell, and TCPP molecules covalently immobilized onto the shell surface. The silica shell is employed a rigid spacer for precisely tuning the distance between AuNR and TCPP and an optimum fluorescence enhancement is obtained. Due to the quenching effect of Cu²⁺, the copper porphyrin (TCPP‐Cu²⁺) results in a weak fluorescence. In the presence of PPi, the strong affinity between Cu²⁺ and PPi can promote the disassembly of the turn‐off state of TCPP‐Cu²⁺ complexes, and therefore the fluorescence can be readily restored. By virtue of the amplified fluorescence signal imparted by PEF, this nanosensor obtains a detection limit of 820 × 10^?9m of PPi with a good selectivity over several anions, including phosphate. Additionally, the potential applicability of this sensor in cell imaging is successfully demonstrated.     

Photo‐ and pH‐Triggered Release of Anticancer Drugs from Mesoporous Silica‐Coated Pd@Ag Nanoparticles

A smart drug delivery system integrating both photothermal therapy and chemotherapy for killing cancer cells is reported. The delivery system is based on a mesoporous silica‐coated Pd@Ag nanoplates composite. The Pd@Ag nanoplate core can effectively absorb and convert near infrared (NIR) light into heat. The mesoporous silica shell is provided as the host for loading anticancer drug, doxorubicin (DOX). The mesoporous shell consists of large pores, ～10 nm in diameter, and allows the DOX loading as high as 49% in weight. DOX loaded core–shell nanoparticles exhibit a higher efficiency in killing cancer cells than free DOX. More importantly, DOX molecules are loaded in the mesopores shell through coordination bonds that are responsive to pH and heat. The release of DOX from the core‐shell delivery vehicles into cancer cells can be therefore triggered by the pH drop caused by endocytosis and also NIR irradiation. A synergistic effect of combining chemotherapy and photothermal therapy is observed in our core‐shell drug delivery system. The cell‐killing efficacy by DOX‐loaded core–shell particles under NIR irradiation is higher than the sum of chemotherapy by DOX‐loaded particles and photothermal therapy by core–shell particles without DOX.     

Ag@SiO_2核壳结构颗粒的可控合成与性能研究

首先通过柠檬酸钠还原法制备了粒径分别约为20nm和50nm的银纳米颗粒。采用改进的Stber法在银颗粒外面包裹二氧化硅,通过控制正硅酸四乙酯(TEOS)的滴加时间和滴加量控制壳层生长来制备Ag@SiO_2核壳结构颗粒,采用TEM,红外、紫外–可见光光谱分析等方法系统表征了样品形貌、结构及光学性能。结果表明,采用上述方法成功制备了壳层厚度分别为16,22,60,69,79nm的核壳结构颗粒。光谱分析结果指出,该类核壳结构颗粒表面等离子共振吸收峰位对于分散介质相当敏感。     

Cover Picture: Encapsulation of Water‐Immiscible Solvents in Polyglutamate/ Polyelectrolyte Nanocontainers (Adv. Funct. Mater. 8/2007)

A novel approach for encapsulation of hydrophobic materials into hydrophilic multifunctional shells is based on combining ultrasonic techniques and layer‐by‐layer protocols. Polyglutamate/polyelectrolyte nanocontainers of 600 nm size loaded with hydrophobic tetraphenylporphin are fabricated in work reported by Dmitri Shchukin and co‐workers on p. 1273. The hydrophobic core of the nanocontainers can encapsulate a huge variety of water‐insoluble drugs and the outer hydrophilic polyelectrolyte shell has controlled permeability and multifunctionality. A novel approach for encapsulation of hydrophobic materials into a hydrophilic multifunctional shell is presented, based on combining an ultrasonic technique and a layer‐by‐layer protocol. Polyglutamate/polyethyleneimine (PEI)/polyacrylic acid (PAA) and polyglutamate/PEI/PAA/silver nanocontainers loaded with a hydrophobic dye, 5,10,15,20‐tetraphenylporphin, dissolved in toluene, are fabricated. Uniform, stable, and monodisperse polyglutamate/PEI/PAA nanocontainers of about 600 nm are obtained. The hydrophobic core of the nanocontainers might contain a huge variety of water‐insoluble drugs and the outer polyelectrolyte shell may provide controlled permeability and desired multifunctionality. Confocal fluorescence microscopy and scanning electron microscopy are employed for the characterization of the resulting nanocontainers. Using sodium dodecyl sulfate as surfactant, the amount of nanocontainers, their monodispersity, and stability can be increased dramatically.     

Brilliant Pitaya‐Type Silica Colloids with Central–Radial and High‐Density Quantum Dots Incorporation for Ultrasensitive Fluorescence Immunoassays

Creating secondary nanostructures from fundamental building blocks with simultaneous high loading capacity and well‐controlled size/uniformity, is highly desired for nanoscale synergism and integration of functional units. Here a novel strategy is reported for hydrophobic quantum dots (QDs) assembley with porous templates, to form pitaya‐type fluorescent silica colloids with densely packed and intact QDs throughout the silica matrix. The mercapto‐terminated dendritic silica spheres with highly accessible central–radial pores and metal‐affinity interior surface, are adopted as a powerful absorbent host for direct immobilization of QDs from organic phase with high loading capacity. The alkylsilane mediated silica encapsulation prevents QDs' optical degradation induced by ligand exchange and favors the homogeneous silica shell formation. These multiple QD embedded silica spheres exhibit good compatibility for different colored QDs with well‐preserved fluorescence, high colloidal/optical stability, and versatile surface functionality. It is demonstrated that after integration with a lateral flow strip platform, these silica colloids provide an ultrasensitive, specific, and robust immunoassay for C‐reaction protein in clinical samples as promising fluorescent reporters.     

Biopebbles: DNA‐Functionalized Core–Shell Silica Nanospheres for Cellular Uptake and Cell Guidance Studies

The development of a versatile class of silica nanoparticles for cell studies is reported. The particles contain a fluorescent dye‐encoded core and a single‐stranded DNA oligonucleotide‐displaying shell. They are accessible in arbitrary size and color through robust protocols for Stöber‐based colloidal synthesis and sturdy chemical surface functionalization. Silica particles in the size range of 100 nm to 1.5 µm diameter containing fluorescein, Cy3 oder Cy5 dye‐encoded cores are synthesized and functionalized with DNA oligonucleotides. These silica biopebbles are conveniently traceable by microscopy and have a high affinity to live cells, which makes them ideal for cell uptake studies, as demonstrated for MCF7 and A431 cancer cells. The biopebbles can be utilized as building blocks for the self‐assembled formation of arbitrary surface patterns on glass substrates. With these architectures, the privileged internalization of the biopebbles can be exploited for improved adhesion and guidance of cells because the particles are no longer ingested by adhered cells due to their physical connection with the solid support. It is believed that the biopebble approach will be useful for a variety of applications, fundamental studies in cell biology and tissue engineering.     

Silica‐Coated Manganese Oxide Nanoparticles as a Platform for Targeted Magnetic Resonance and Fluorescence Imaging of Cancer Cells

Monodisperse silica‐coated manganese oxide nanoparticles (NPs) with a diameter of ～35 nm are synthesized and are aminated through silanization. The amine‐functionalized core–shell NPs enable the covalent conjugation of a fluorescent dye, Rhodamine B isothiocyanate (RBITC), and folate (FA) onto their surface. The formed Mn₃O₄@SiO₂(RBITC)–FA core–shell nanocomposites are water‐dispersible, stable, and biocompatible when the Mn concentration is below 50 µg mL^?1 as confirmed by a cytotoxicity assay. Relaxivity measurements show that the core–shell NPs have a T₁ relaxivity (r₁) of 0.50 mM ^?1 s^?1 on the 0.5 T scanner and 0.47 mM ^?1 s^?1 on the 3.0 T scanner, suggesting the possibility of using the particles as a T₁ contrast agent. Combined flow cytometry, confocal microscopy, and magnetic resonance imaging studies show that the Mn₃O₄@SiO₂(RBITC)–FA nanocomposites can specifically target cancer cells overexpressing FA receptors (FARs). Findings from this study suggest that the silica‐coated Mn₃O₄ core–shell NPs could be used as a platform for bimodal imaging (both magnetic resonance and fluorescence) in various biological systems.     

Synthesis,Characterization, and Application of Antibody Functionalized Fluorescent Silica Nanoparticles

Fluorescent silica nanoparticles (FSNs) are prepared by incorporating dye into a mesoporous silica nanoparticle (MSN) synthesis procedure. FSNs containing sulforhodamine B, hydrophobically modified sulforhodamine B, and Cascade Blue hydrazide are made. The MSN‐based FSNs do not leach dye under simulated physiological conditions and have strong, stable fluorescence. FSNs prepared with sulforhodamine B are compared to FSNs prepared with hydrophobically modified sulforhodamine B. The data indicate that FSNs prepared with sulforhodamine B are equally as stable but twice as fluorescent as particles made with hydrophobically modified sulforhodamine B. The fluorescence of a FSN prepared with sulforhodamine B is 10 times more intense than the fluorescence of a 4.5 nm core–shell CdSe/ZnS quantum dot. For diagnostic applications, a method to selectively and covalently bind antibodies to the surface of the FSNs is devised. FSNs that are functionalized with antibodies specific for Neisseria gonorrhoeae specifically bind to Neisseria gonorrhoeae in flow cytometry experiments, thus demonstrating the functionality of the attached antibodies and the potential of MSN‐based FSNs to be used in diagnostic applications.     

Hollow Two‐Layered Chiral Nanoparticles Consisting of Optically Active Helical Polymer/Silica: Preparation and Application for Enantioselective Crystallization

This article reports for the first time a novel category of hollow organic@inorganic hybrid two‐layered nanoparticles (NPs), in which the inner layer is formed by optically active helical polyacetylene, and the outer layer by silica. Such NPs show remarkable optical activity and are successfully used for enantioselective crystallization. To prepare such NPs, n‐butyl acrylate undergoes radical polymerization to first form poly(n‐butyl acrylate) (PBA) cores two shells by catalytic polymerization of substituted acetylene and sol–gel approach of TEOS (tetraethyl orthosilicate), respectively. Removal of the PBA cores provides the expected hollow core/shell NPs. The intense dircular dichroism (CD) effects demonstrate that the hollow chiral NPs possess considerable optical activity, arising from the helical substituted polyacetylenes forming the inner layer. The hollow NPs are further used as chiral templates to induce enantioselective crystallization of racemic alanines, demonstrating the significant potential applications of the hollow chiral NPs in chiral technologies. Also of particular significance is the detailed process of the induced crystallization observed by TEM. The strategy for preparing the hollow hybrid chiral NPs should be highlighted since it combines free radical polymerization and catalytic polymerization with sol–gel process in a single system, by which numerous advanced materials will be accessible.     

Near‐Infrared Fluorescent Silica/Porphyrin Hybrid Nanorings for In Vivo Cancer Imaging

Ring‐shaped silica nanoparticles are synthesized with a high tetrakis(4‐carboxyphenyl)porphyrin (TCPP) content or silica/TCPP hybrid nanorings (HNRs) using a one‐pot sol‐gel reaction with a TCPP‐binding silica precursor for fluorescence imaging of tumor. The shape of the HNRs is a reflection of abundant ring‐shaped TCPP aggregates in the silica matrix. The HNRs are of a size that makes them susceptible to the enhanced permeability and retention effect. For comparison, the TCPP‐doped silica nanoparticles are synthesized using a conventional method. The nanoparticles are spherical in shape because little TCPP is contained in the silica matrix and are designated as TCPP‐containing silica nanospheres (NSs). The absorption bands of the HNRs shift by about 20 nm toward longer wavelengths compared with the TCPP bands. This redshift leads the excitation wavelength of the HNRs into the near‐infrared (NIR) region. Therefore, the HNRs are excited by NIR light to emit strong fluorescence, although the NSs emit no fluorescence. The PEGylated HNRs (PEG‐HNRs) are uncharged and possess a significantly longer blood circulation time than PEG‐NSs. The PEG‐HNRs accumulate in tumor through multiple factors including their size, uncharged surface, unique shape, and long circulation time in blood, resulting in the acquisition of clear images of tumor.     

Multifunctional Core/Shell Nanoparticles Self‐Assembled from pH‐Induced Thermosensitive Polymers for Targeted Intracellular Anticancer Drug Delivery

Core/shell nanoparticles that display a pH‐sensitive thermal response, self‐assembled from the amphiphilic tercopolymer, poly(N‐isopropylacrylamide‐co‐N,N‐dimethylacrylamide‐co‐10‐undecenoic acid) (P(NIPAAm‐co‐DMAAm‐co‐UA)), have recently been reported. In this study, folic acid is conjugated to the hydrophilic segment of the polymer through the free amine group (for targeting cancer cells that overexpress folate receptors) and cholesterol is grafted to the hydrophobic segment of the polymer. This polymer also self‐assembles into core/shell nanoparticles that exhibit pH‐induced temperature sensitivity, but they possess a more stable hydrophobic core than the original polymer P(NIPAAm‐co‐DMAAm‐co‐UA) and a shell containing folate molecules. An anticancer drug, doxorubicin (DOX), is encapsulated into the nanoparticles. DOX release is also pH‐dependent. DOX molecules delivered by P(NIPAAm‐co‐DMAAm‐co‐UA) and folate‐conjugated P(NIPAAm‐co‐DMAAm‐co‐UA)‐g‐cholesterol nanoparticles enter the nucleus more rapidly than those transported by P(NIPAAm‐co‐DMAAm)‐b‐poly(lactide‐co‐glycolide) nanoparticles, which are not pH sensitive. More importantly, these nanoparticles can recognize folate‐receptor‐expressing cancer cells. Compared to the nanoparticles without folate, the DOX‐loaded nanoparticles with folate yield a greater cellular uptake because of the folate‐receptor‐mediated endocytosis process, and, thus, higher cytotoxicity results. These multifunctional polymer core/shell nanoparticles may make a promising carrier to target drugs to cancer cells and release the drug molecules to the cytoplasm inside the cells.     

Microporosity‐Controlled Synthesis of Heteroatom Codoped Carbon Nanocages by Wrap‐Bake‐Sublime Approach for Flexible All‐Solid‐State‐Supercapacitors

Heteroatom‐doped carbon nanomaterials with high surface area and tunable microporosity are important but they generally require difficult and multistep syntheses. Herein, a simple and straightforward strategy is introduced that involves a wrap‐bake‐sublime approach to synthesize microporosity controlled and heteroatom codoped carbon nanocages. A zinc‐containing zeolitic imidazolate framework (ZIF‐8) core is wrapped in a cross‐linked oligomer containing nitrogen and phosphorus, oligo(cyclotriphosphazene‐co‐hexahydroxytriphenylene) (OCHT). As‐synthesized core–shell ZIF‐8‐OCHT nanoparticles are baked at high temperatures to sublimate zinc through OCHT shell, resulting in a porous structure. Meanwhile, hollow cavities are introduced into N,P codoped carbon nanocages (NPCNs) via the sacrificial nature of ZIF‐8 template. The microporosity is finely tuned by controlling thickness of the OCHT shell during synthesis of the core–shell nanoparticles, since the sublimation tendency of zinc component at high temperatures depends on the thickness of OCHT shell. A systematic correlation between the electrochemical performance of NPCNs and their microporosity is confirmed. Furthermore, the electrochemical performance of the NPCNs is related to the degree of heteroatom codoping. The approach is successfully scaled‐up without compromising their electrochemical performance. Finally, a symmetric and flexible all‐solid‐state‐supercapacitor with high energy and power density, and a long‐term cycleability is demonstrated (75% capacitance retention after 20 000 cycles).     

Gold Core‐DNA‐Silver Shell Nanoparticles with Intense Plasmonic Chiroptical Activities

The strong plasmonic chiroptical activities of gold core‐DNA‐silver shell nanoparticles (NPs) are reported for the first time, using cytosine‐rich single‐stranded DNA as the template for the guidance of silver shell growth. The anisotropy factor of the optically active NPs at 420 nm reaches 1.93 × 10^?2. Their chiroptical properties are likely induced by the DNA–plasmon interaction and markedly amplified by the strong electromagnetic coupling between the gold core and silver shell.     

Water‐Stable,Magnetic Silica–Cobalt/Cobalt Oxide–Silica Multishell Submicrometer Spheres

A method to produce monodisperse magnetic composite spheres with diameters from less than 100 nm to more than 1 μm in water solution is reported. The spheres consist of a dielectric silica core and a cobalt/cobalt oxide shell which can be protected from further oxidation with an outer shell of silica or, alternatively, they can be covered with the polymer polyvinylpyrrolidone as a stabilizer. The formation of a uniform magnetic shell proceeds with the adsorption of metallic cobalt seeds, produced by the reduction of cobalt chloride with sodium borohydride, on a self‐assembled layer of polyelectrolytes on the silica core. In the second step, an outer silica shell can be formed by the hydrolysis and condensation of (3‐aminopropyl)trimethoxysilane and tetraethoxysilane. The double‐shell composite spheres show excellent sphericity, monodispersity, and a magnetic hysteresis loop at room temperature.