Glutathione (GSH) plays a crucial role in various physiological processes. Therefore, efficient detection of GSH is of great importance. In this study, we present a new and highly efficient ratiometric fluorescent biosensor through one-pot synthesis of coupling the self-assembly of polysaccharide (alginate dialdehyde, ADA)-dipeptide (diphenylalanine, FF) and in situ reduction of gold nanoparticles (Au NPs) simultaneously encapsulating a dye (5-aminofluorescein, FI-NH2) inside to form ADA-Au-FF-dye nanospheres. Because the fluorescence of the dye can be quenched by Au NPs and linearly recovered following the introduction of different GSH concentrations owing to nanometal surface energy transfer on and off, this new ADA-Au-FF-dye hybrid nanosphere-based sensor allows label-free and ratiometric detection of intracellular GSH and other biothiols in a wide linear range, which is of great significance for cancer diagnostics and therapy.

Hollow micro-/nano-spheres with large-through-holes in shells (denoted as HMLS) have demonstrated great potential in biomedical applications owing to the combination of hollow structure and their porous shells. In this review, we provide a comprehensive overview of synthesis methods of HMLS obtained from the template-directed approach, shell-breaking method, Ostwald ripening and galvanic replacement primarily based on the formation mechanism of the large-through-holes in the shell. We further discuss the biomedical applications of HMLS including guest adsorption and encapsulation of proteins, drug/gene delivery, biomedical imaging, and theranostics. We conclude this review with some perspectives on the future research and development of the HMLS with desired morphologies and properties.

Nano drug delivery systems have attracted much research and clinical interest but they remain challenging with respect to developing controllable, nontoxic, biocompatible and biodegradable nanocarriers. Herein, we report the first pH- and glutathione (GSH)-responsive diphenylalanine (FF)-based hybrid spheres using natural alginate dialdehyde (ADA) as the cross-linker to induce self-assembly of FF and an in situ reducer of Au3+ ions into Au nanoparticles (Au NPs). Not only is the synthesis simple and high-yielding, but also these biocompatible hybrid spheres can encapsulate more than 95% of hydrophobic drug (camptothecin, CPT). Moreover, the CPT-loaded carriers are stable under normal physiological environments, and have excellent pH- and GSH-responsive release at pH 5.0 with 10 mM GSH, which is similar to the tumor microenvironment. Also, these nanocarriers can be taken up by cancer cells and have greater cytotoxicity than free drugs. These attributes make nanospheres very promising for drug loading and delivery, and the method may be used for synthesis of other natural nanospheres as delivery systems.

A facile, one-step method to prepare cagelike hollow silica nanospheres with large through-holes (HSNLs) using a lysozyme-assisted O/W miniemulsion technique is presented. The tetraethoxysilane (TEOS)–xylene mixture forms oil droplets which are stabilized by the cationic surfactant cetyltrimethylammonium bromide (CTAB), cosurfactant hexadecane (HD), and protein lysozyme. HSNLs (with diameter of 300–460 nm) with large through-holes (10–30 nm) were obtained directly after ultrasonic treatment and aging. Lysozyme can not only stabilize the oil/water interface, assist the hydrolysis of TEOS, and interact with silica particles to assemble into silica-lysozyme clusters but also contribute to the formation of through-holes due to its hydrophilicity variation at different pH conditions. A possible new mechanism called the interface desorption method is proposed to explain the formation of the through-holes. To confirm the effectiveness of large through-holes in delivering large molecules, bovine serum albumin (BSA, 21 × 4 × 14 nm3) was chosen as a model guest molecule; HSNLs showed much higher loading capacity compared with common hollow mesoporous silica nanospheres (HMSNs). The release of BSA can be well controlled by wrapping HSNLs with a heat-sensitive phase change material (1-tetradecanol). Cell toxicity was also conducted with a Cell Counting Kit-8 (CCK-8) assay to roughly evaluate the feasibility of HSNLs in biomedical applications.Keywords: hollow; large through-holes; lysozyme; oil-in-water miniemulsion; silica;

A series of Au/ZnO hybrid hollow-sphere films were successfully prepared by “hexane–water” interfacial self-assembly of polystyrene (PS)/Au/ZnO nanocomposite spheres as building blocks followed by annealing treatment, and then used to fabricate nanodevices. The morphology and structure of the PS/Au/ZnO nanospheres and the as-transformed Au/ZnO hybrid hollow spheres were characterized by TEM, SEM, HRTEM, XRD, etc. It was found that the maximum responsivity (Rλ) and photocurrent of Au NPs decorated ZnO hollow-sphere nanofilm based nanodevice in the study showed more than 10 times enhancement when illuminated by 340 nm UV light, as compared with that of pure ZnO hollow spheres. Further results demonstrate that high performance of the Au/ZnO hybrid hollow-sphere film based devices are attributed to the strong absorption and scattering of incident light and improved interfacial charge separation owing to the unique structure of the building block.

Multifunctional PNIPAM/Fe3O4–ZnS hybrid hollow spheres integrating magnetism, luminescence, and temperature responses into one single entity have been successfully fabricated via a facile method. First, the cross-linked Poly (N-isopropylacrylamide) (PNIPAM) hollow spheres were synthesized via a classical method, named one-pot “self-removing” process. Then, Fe3O4 and ZnS nanoparticles were in situ precipitated on the surface of the PNIPAM hollow spheres. The PNIPAM/Fe3O4–ZnS hybrid hollow spheres exhibit magnetic property, which indicates the potential application in drug targeting. In addition, ZnS nanoparticles in the shell play an important role as a luminescent label for tracking the drug delivery. Meanwhile, the existence of PNIPAM provides a thermosensitive property. All these results indicate that the obtained composite can be expected to be used as a smart drug delivery material.Graphical abstractHighlights► PNIPAM/Fe3O4–ZnS hybrid hollow spheres were prepared with a facile method. ► Concentration of Fe2+, Zn2+, TAA, and HMTA determined the morphology of the nanocomposite spheres. ► The obtained hybrid hollow spheres possessed magnetic, luminescent, and thermosensitive properties.

This paper presents a facile method to synthesize monodisperse SrTiO3 hollow spheres with one or two openings through a template-assisted approach. These hollow spheres were further self-assembled into densely packed nanofilms at a “hexane–water” interface. TEM, SEM, HRTEM, XRD, etc., were employed to characterize the morphology and structure of the SrTiO3 hollow spheres as well as the corresponding nanofilms. The nanofilm-based photodevice displayed considerably higher sensitivity to UV than visible light and dark.

This paper presents a novel and facile method to fabricate hollow silica/sliver (SiO2/Ag) nanocomposite spheres. In this approach, the monodisperse hollow SiO2 colloids bearing quantenary ammonium groups were prepared by dispersion polymerization combined sol–gel process and used as templates. The Ag+ ions were first adsorbed onto the surfaces of the hollow SiO2 beads via electrostatic interaction and then in situ reduced by the deprotonated silanol groups of the hollow SiO2 beads, no extra reducing agents or catalysts were added during the reduction process. TEM, SEM and EDX analyses indicated that Ag nanoparticles were successfully deposited onto the surfaces of hollow SiO2 beads. Some influencing parameters, such as the amount of quantenary ammonium groups in the inner wall of hollow SiO2 colloids, Ag+ ions concentration and reaction temperature, on the deposition of Ag nanoparticles onto SiO2 colloids were investigated. Preliminary antibacterial tests indicated that these hollow nanocomposite spheres showed excellent antibacterial ability.Graphical abstractTEM image of the silica/sliver (SiO2/Ag) nanocomposite spheres obtained from self-reduction of monodisperse hollow SiO2 colloids bearing quantenary ammonium groups as templates.Highlights► The Ag+ ions were in situ reduced by the deprotonated silanol groups of the hollow SiO2 beads. ► No extra reducing agents or catalysts were added during the reduction process. ► These hollow nanocomposite spheres showed excellent antibacterial ability.

This paper presents a one-step method to fabricate PS/TiO2 nanocomposite particles via miniemulsion polymerization technique. In this approach, styrene (St) and acetylacetone (Acac) chelated tetra-n-butyl titanate (TBT) were confined in the miniemulsion droplets with the aid of cationic surfactant cetyl trimethyl ammonium bromide (CTAB) and co-stabilizer hexadecane (HD). During the polymerization of St, TBT diffused towards the surface of the miniemulsion droplets owing to its hydrophilicity and yielded TiO2 particles via a sol–gel process. With the electrostatic interaction between the positively charged CTAB and negatively charged Ti-OH, TiO2 particles were coated onto the PS cores to form PS/TiO2 nanocomposite particles.Raspberry-like PS/TiO2 nanocomposite particles have been prepared through a one-step method based on miniemulsion polymerization. The polymerization of styrene and sol–gel reaction of tetra-n-butyl titanate occurred simultaneously inside droplets.

This article presents a novel miniemulsion-combined sol–gel process to fabricate TiO2–SiO2 hybrid capsules. In this approach, the oil phase composed of acetylacetone (Acac) modified titanium (IV) butoxide (TBT), dimethyl benzene (DB) and hexadecane (HD) is confined in the miniemulsion droplet microreactors with the aid of a cationic emulsifier hexadecyltrimethylammonium bromide (CTAB). Then, a silica layer was coated onto the miniemulsion droplets by the co-condensation of amino-silane and tetraethyl silicate (TEOS). At the same time, TBT in the miniemulsion droplets diffused to the O/W interface and then initiated the sol–gel reaction, hence TiO2–SiO2 hybrid shell with TiO2 colloids loading inside formed. TEM, FTIR, EDX and XPS indicated that TiO2–SiO2 hybrids possess hollow-like structure, with small titania colloids loaded in the titania/silica hybrid shells. Some influencing parameters, such as the concentrations of TBT in the oil droplet, the content of amino-silane in the silica precursor, on the morphology of the TiO2–SiO2 hybrid capsules were investigated. UV–vis spectra and dye degradation experiments showed that the polyurethane films doped with these hybrid colloids had a very good UV-protective property.

Raspberry-like polymer/silica nanocomposite microspheres were prepared by emulsifier-free copolymerization of styrene (St) with butyl acrylate (BA) in the presence of 20 nm silica nanoparticles in water/acetone media. A cationic monomer, 2-(methacryloyl)ethyltrimethylammonium chloride (MTC), was used as comonomer and nanosilica particles were adsorbed onto the growing latex core via the electrostatic interaction between negatively charged silica particles and positively charged polymer particles. The average particle sizes and the final silica contents of the nanocomposite microspheres ranged from 200 to 500 nm and 20 to 40 wt%, respectively, depending on the reaction conditions. The solid content of the obtained dispersions could be adjusted between 10 and 25 wt%. The influence of some synthetic parameters, for instance, the ratio of acetone/water, initial silica amount, the mass ratio of the St/BA, MTC, and the APS concentration on the polymerization stability, the average particle size, silica content, and morphology of the composite microspheres, were studied here in detail. It was found that the addition of acetone to the continuous phase resulted in smaller particle sizes and for the lower dielectric medium electrostatic repulsion becomes larger; hence coagulative nucleation is reduced compared to that in aqueous media.The raspberry-like polymer/silica nanocomposite microspheres were prepared by emulsifier-free copolymerization in the presence of 20 nm silica nanoparticles in a mixed water/acetone solvent.

Hollow micro-/nano-spheres with large-through-holes in shells (denoted as HMLS) have demonstrated great potential in biomedical applications owing to the combination of hollow structure and their porous shells. In this review, we provide a comprehensive overview of synthesis methods of HMLS obtained from the template-directed approach, shell-breaking method, Ostwald ripening and galvanic replacement primarily based on the formation mechanism of the large-through-holes in the shell. We further discuss the biomedical applications of HMLS including guest adsorption and encapsulation of proteins, drug/gene delivery, biomedical imaging, and theranostics. We conclude this review with some perspectives on the future research and development of the HMLS with desired morphologies and properties.