The successful cancer eradication in a noninvasive manner is the ultimate objective in the fight against cancer. As a “bloodless scalpel,” high-intensity focused ultrasound (HIFU) is regarded as one of the most promising and representative noninvasive therapeutic modalities for cancer surgery. However, large-scale clinical applications of HIFU are still in their infancy because of critical efficiency and safety issues which remain to be solved. Fortunately, recently developed nanobiotechnology provides an alternative efficient approach to improve such important issues in HIFU, especially for cancer therapy. This Research News presents the very recent exciting progresses on the elaborate design and fabrication of organic, inorganic, and organic/inorganic hybrid nanoparticles for enhancing the HIFU ablation efficiency against tumor tissues. It is highly expected that this Research News can arouse more extensive research enthusiasm on the development of functional nanomaterials for highly efficient HIFU-based synergistic therapy, which will give a promising noninvasive therapeutic modality for the successful cancer therapy with minimal damage to surrounding normal tissues, due to the noninvasive and site-specific therapeutic features of HIFU.

Hollow-structured mesoporous materials (HMMs), as a kind of mesoporous material with unique morphology, have been of great interest in the past decade because of the subtle combination of the hollow architecture with the mesoporous nanostructure. Benefitting from the merits of low density, large void space, large specific surface area, and, especially, the good biocompatibility, HMMs present promising application prospects in various fields, such as adsorption and storage, confined catalysis when catalytically active species are incorporated in the core and/or shell, controlled drug release, targeted drug delivery, and simultaneous diagnosis and therapy of cancers when the surface and/or core of the HMMs are functionalized with functional ligands and/or nanoparticles, and so on. In this review, recent progress in the design, synthesis, functionalization, and applications of hollow mesoporous materials are discussed. Two main synthetic strategies, soft-templating and hard-templating routes, are broadly sorted and described in detail. Progress in the main application aspects of HMMs, such as adsorption and storage, catalysis, and biomedicine, are also discussed in detail in this article, in terms of the unique features of the combined large void space in the core and the mesoporous network in the shell. Functionalization of the core and pore/outer surfaces with functional organic groups and/or nanoparticles, and their performance, are summarized in this article. Finally, an outlook of their prospects and challenges in terms of their controlled synthesis and scaled application is presented.

As one of the most important clean energy sources, proton exchange membrane fuel cells (PEMFCs) have been a topic of extensive research focus for decades. Unfortunately, several critical technique obstacles, such as the high cost of platinum electrode catalysts, performance degradation due to the CO poisoning of the platinum anode, and carbon corrosion by oxygen in the cathode, have greatly impeded its commercial development. A prototype of a single PEMFC catalyzed by a mesostructured platinum-free WO₃/C anode and a mesostructured carbon-free Pt/WC cathode catalysts is reported herein. The prototype cell exhibited 93 % power output of a standard PEMFC using commercial Pt/C catalysts at 50 and 70 °C, and more importantly, CO poisoning-free and carbon corrosion-resistant characters of the anode and cathode, respectively. Consequently, the prototype cell demonstrated considerably enhanced cell operation durability. The mesostructured electrode catalysts are therefore highly promising in the future development and application of PEMFCs.

Paramagnetic gadolinium (Gd-III)-ion-doped upconversion nanoparticles (UCNPs) are attractive optical-magnetic molecule imaging probes and are a highly promising nanoplatform for future theranostic nanomedicine design. However, the related relaxivity mechanism of this contrast agent is still not well understood and no significant breakthrough in relaxivity enhancement has been achieved. Here, the origin and optimization of both the longitudinal (r₁) and transverse (r₂) relaxivities are investigated using models of water soluble core@shell structured Gd³⁺-doped UCNPs. The longitudinal relaxivity enhancement of the nanoprobe is demonstrated to be co-contributed by inner-and outer-sphere mechanisms for ligand-free probes, and mainly by outer-sphere mechanism for silica-shielded probes. The origin of the transverse relaxivity is inferred to be mainly from an outer-sphere mechanism regardless of surface-coating, but with the r₂ values highly related to the surface-state. Key factors that influence the observed relaxivities and r₂/r₁ ratios are investigated in detail and found to be dependent on the thickness of the NaGdF₄ interlayer and the related surface modifications. A two orders of magnitude (105-fold) enhancement in r₁ relaxivity and 18-fold smaller r₂/r₁ ratio compared to the first reported values are achieved, providing a new perspective for magnetic resonance (MR) sensitivity optimization and multimodality biological imaging using Gd³⁺-doped UCNPs.

A novel drug-formulation protocol is developed to solve the delivery problem of hydrophobic drug molecules by using inorganic mesoporous silica nanocapsules (IMNCs) as an alternative to traditional organic emulsions and liposomes while preserving the advantages of inorganic materials. The unique structures of IMNCs are engineered by a novel fluoride-silica chemistry based on a structural difference-based selective etching strategy. The prepared IMNCs combine the functions of organic nanoemulsions or nanoliposomes with the properties of inorganic materials. Various spherical nanostructures can be fabricated simply by varying the synthetic parameters. The drug loading amount of a typical highly hydrophobic anticancer drug-camptothecin (CPT) in IMNCs reaches as high as 35.1 wt%. The intracellular release of CPT from carriers is demonstrated in situ. In addition, IMNCs can play the role of organic nanoliposome (multivesicular liposome) in co-encapsulating and co-delivering hydrophobic (CPT) and hydrophilic (doxorubicin, DOX) anticancer drugs simultaneously. The co-delivery of multi-drugs in the same carrier and the intracellular release of the drug combinations enables a drug delivery system with efficient enhanced chemotherapeutic effect for DOX-resistant MCF-7/ADR cancer cells. The special IMNCs-based “inorganic nanoemulsion”, as a proof-of-concept, can also be employed successfully to encapsulate and deliver biocompatible hydrophobic perfluorohexane (PFH) molecules for high intensity focused ultrasound (HIFU) synergistic therapy ex vivo and in vivo. Based on this novel design strategy, a wide range of inorganic material systems with similar “inorganic nanoemulsion or nanoliposome” functions will be developed to satisfy varied clinical requirements.

Upconverting nanoparticles (UCNPs) with fascinating properties hold great potential as nanotransducers for solving the problems that traditional photodynamic therapy (PDT) has been facing. In this report, by using well-selected bifunctional gadolinium (Gd)-ion-doped UCNPs and water-soluble methylene blue (MB) combined with the water-in-oil reverse microemulsion technique, we have succeeded in developing a new kind of UCNP/MB-based PDT drug, NaYF₄:Er/Yb/Gd@SiO₂(MB), with a particle diameter less than 50 nm. Great efforts have been made to investigate the drug-formation mechanism and provide detailed physical and photochemical characterizations and the potential structure optimization of the as-designed PDT drug. We envision that such a PDT drug will become a potential theranostic nanomedicine for future near-infrared laser-triggered photodynamic therapy and simultaneous magnetic/optical bimodal imaging.

Here we report the design and controlled synthesis of monodisperse and precisely size-controllable UCNP@mSiO₂ nanocomposites smaller than 50 nm by directly coating a mesoporous silica shell (mSiO₂) on upconversion nanocrystals NaYF₄:Tm/Yb/Gd (UCNPs), which can be used as near-infrared fluorescence and magnetic resonance imaging (MRI) agents and a platform for drug delivery as well. Some key steps such as transferring hydrophobic UCNPs to the water phase by using cetyltrimethylammonium bromide (CTAB), removal of the excess amount of CTAB, and temperature-controlled ultrasonication treatment should be adopted and carefully monitored to obtain uniform upconversion core/mesoporous silica shell nanocomposites. The excellent performance of the core–shell-structured nanocomposite in near-infrared fluorescence and magnetic resonance imaging was also demonstrated.

Gadolinium (Gd) doped upconversion nanoparticles (UCNPs) have been well documented as T₁-MR and fluorescent imaging agents. However, the performance of Gd³⁺ ions located differently in the crystal lattice still remains debatable. Here, a well-designed model was built based on a seed-mediated growth technique to systematically probe the longitudinal relaxivity of Gd³⁺ ions within the crystal lattice and at the surface of UCNPs. We found, for the first time, a nearly 100% loss of relaxivity of Gd³⁺ ions buried deeply within crystal lattices (> 4 nm), which we named a “negative lattice shielding effect” (n-LSE) as compared to the “positive lattice shielding effect” (p-LSE) for the enhanced upconversion fluorescent intensity. As-observed n-LSE was further found to be shell thickness dependent. By suppressing the n-LSE as far as possible, we optimized the UCNPs' structure design and achieved the highest r₁ value (6.18 mM⁻¹s⁻¹ per Gd³⁺ ion) among previously reported counterparts. The potential bimodal imaging application both in vitro and in vivo of as-designed nano-probes was also demonstrated. This study clears the debate over the role of bulk and surface Gd³⁺ ions in MRI contrast imaging and paves the way for modulation of other Gd-doped nanostructures for highly efficient T₁-MR and upconversion fluorescent bimodal imaging.

A novel in situ decomposition/reduction approach is developed to manu­facture hollow core, magnetic, and mesoporous double-shell nanostructures (HMMNSs) via in situ decomposition and reduction of a β-FeOOH nanorod core and organosilicate-incorporated silica-shell precursor. The formed HMMNSs are then aminated by silanization for further covalent conjugation to rhodamine B isothiocyanate (RBITC) and poly(ethylene glycol) (PEG) chains. The resultant RBITC-grafted and PEGylated nanocomposites (HMMNS–R/Ps) have excellent blood compatibility and very low cytotoxicity towards HeLa and MCF-7 cells, and can be taken up by cancer cells effectively in a dose-dependent manner, as confirmed by in vitro flow cytometry, confocal luminescence imaging, and magnetic resonance imaging (MRI) studies. In vivo MRI studies coupled with Prussian blue staining of slides from different organs show that the nanocomposites preferentially accumulate in liver and spleen after intravenous injection, which suggests a potential application of the nanocomposites as MRI contrast agents. Importantly, the HMMNS–R/P nanocomposites show high loading capacity for water-insoluble anticancer drugs (docetaxel or camptothecin) owing to the presence of a large inner cavity and enhanced surface area and pore volume. Furthermore, the drug-loaded nanocomposites exhibit greater cytotoxicity than the corresponding free drugs. These results confirm that the HMMNS–R/P nanocomposites are promising candidates for simultaneous bioimaging and drug delivery.

A general polyelectrolyte-mediated self-assembly technique is adopted to prepare multifunctional mesoporous nanostructures as an effective biological bimodal imaging probe and magnetically targeted anticancer drug (doxorubicin) delivery systems (DDSs). A positively charged polyelectrolyte (PAH) and negatively charged fluorescent quantum dots (QDs) are successfully assembled onto the surface of ellipsoidal Fe₃O₄@SiO₂@mSiO₂ composite nanostructures to combine the merits of tunable fluorescent/magnetic properties, mesoporous nanostructures for drug loading, and the uniform ellipsoidal morphology for enhanced uptake by cancer cells. The resultant nanoellipsoids are homogeneously coated with four layers of PAH/QDs, with an additional PAH layer to make the ellipsoidal surface positively charged. This acts to enhance cellular uptake, which is driven by electrostatic interactions between the positive nanoparticle surface and the negative cell surface. The high biocompatibility of the achieved multifunctional nanoellipsoids is demonstrated by a cell-cytotoxicity assay, hemolyticity against human red blood cells, and coagulation evaluation of fresh human blood plasma after exposure to the nanoparticles. Moreover, confocal microscopy and bio-TEM observations show that the cell uptake of nanocarriers is dose-dependent, and the nanoparticles accumulate mostly in the cytoplasm. The excellent capability of the nanocarriers as contrast agents for MRI is demonstrated by the relatively high r₂ value (143 mM⁻¹s⁻¹) and preliminary in vivo characterization. More importantly, the doxorubicin-loaded DDSs show higher cytotoxicity than the free doxorubicin drug as contributed by the intracellular release pathway of doxorubicin from the DDSs, indicating the potential application of the obtained multifunctional mesoporous nanoellipsoids as highly effective bimodal imaging probes and DDSs for cancer diagnosis and chemotherapy, simultaneously.

Novel, thiol-functionalized, and superparamagnetic, silica composite nanospheres (SH-SSCNs) with diameters smaller than 100 nm are successfully fabricated through the self-assembly of Fe₃O₄ nanoparticles and polystyrene₁₀₀-block-poly(acrylic acid)₁₆ and a subsequent sol-gel process. The size and magnetic properties of the SH-SSCNs can be easily tuned by simply varying the initial concentrations of the magnetite nanoparticles in the oil phase. By incorporating fluorescent dye molecules into the silica network, the composite nanospheres can be further fluorescent-functionalized. The toxicity of the SH-SSCNs is evaluated by choosing three typical cell lines (HUVEC, RAW264.7, and A549) as model cells, and no toxic effects are observed. It is also demonstrated that SH-SSCNs can be used as a new class of magnetic resonance imaging (MRI) probes, having a remarkably high spin–spin (T₂) relaxivity (r₂* = 176.1 mM⁻¹ S⁻¹). The combination of the sub-100-nm particle size, monodispersity in aqueous solution, superparamagnetism, and fluorescent properties of the SH-SSCNs, as well as the non-cytotoxicity in vitro, provides a novel and potential candidate for an earlier MRI diagnostic method of cancer.

Mesoporous silica nanospheres (MPNSs) were synthesized by the sol–gel method and were investigated by X-ray diffraction, nitrogen sorption, and transmission electron microscopy. The analyses showed that the MPNSs were highly dispersed, with a diameter range of 50–250 nm. Further, the polycation poly(allylamine hydrochloride) was coated on silica MPNSs to form a positively charged surface and to facilitate the loading of DNA molecules. The composite was successfully used as a intercellular carrier of DNA molecules, and this was confirmed by agarose gel electrophoresis and confocal laser scanning microscopy. Evidently, this composite has potential to be used as a carrier for a DNA delivery system. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009

Mesoporous bioactive glass (MBG) and composite microspheres with MBG particles embedded in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) matrix have been prepared and used to load gentamicin (GS). The in vitro drug release experiments from both MBG and composite microspheres were conducted in distilled water and phosphate buffered saline (PBS) solution at 37°C for more than 30 days. In both water and PBS, GS release from the MBG was very fast with about 60 wt % of the loaded drug released in the first 24 h, and more than 80 wt % released in two days. MBG/PLGA composite microspheres showed an initial release of about 33 wt % in the first day, and 48 wt % in 2 days, and a subsequent sustained release lasting for more than 4 weeks in PBS. MBG/PLGA composite microspheres may be used as an alternative drug release system, especially as a bone void filler for bone repair due to their combined advantages of sustained release of antibiotics and apatite-forming ability. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009

Oleic acid stabilized superparamagnetic iron oxide nanoparticles (SPION) were selected as the cores for fabrication of sub-50-nm monodisperse single-loaded SPION@SiO₂ core–shell nanostructures. Parameters that influence the formation of SPION@SiO₂ in the water-in-oil reverse microemulsion system have been systematically investigated. The sufficiently high concentration of well-dispersed SPION, together with an appropriately low injection rate of tetraethoxysilane, were found to be the keys to efficiently prevent the homogeneous nucleation of silica and obtain a high-quality single-loaded core–shell nanocomposite. A more detailed mechanism for incorporating oleic acid capped inorganic functional nanoparticles into silica is proposed on the basis of previous reports and our new experimental results. Finally, the as-synthesized SPION@SiO₂ nanospheres are exploited as an MRI-enhanced contrast agent, and their contrast effect in solution is tested by using a clinical MRI instrument.

Hollow mesoporous carbon spheres with magnetic cores are directly replicated from hollow mesoporous aluminosilicate spheres with hematite cores by a simple incipient-wetness impregnation technique. The amount of magnetic cores and the saturation magnetization value can be easily tuned by changing the concentration of iron nitrate solution used in the synthesis procedure. As-prepared hollow mesoporous carbon spheres with magnetic cores are used as separable bilirubin adsorbents and show very good adsorptive properties. The characteristics of as-prepared composites are examined by XRD, N₂ sorption, TEM, vibrating-sample magnetometry, and UV/Vis spectroscopy.

A novel kind of rattle-type hollow magnetic mesoporous sphere (HMMS) with Fe₃O₄ particles encapsulated in the cores of mesoporous silica microspheres has been successfully fabricated by sol–gel reactions on hematite particles followed by cavity generation with hydrothermal treatment and H₂ reduction. Such a structure has the merits of both enhanced drug-loading capacity and a significant magnetization strength. The prepared HMMSs realize a relatively high storage capacity up to 302 mg g⁻¹ when ibuprofen is used as a model drug, and the IBU–HMMS system has a sustained-release property, which follows a Fick's law.

A facile method has been developed to synthesize nanoporous manganese and nickel oxides with polyhedron particle morphologies, high surface areas and narrow pore distributions by controlled thermal decomposition of the oxalate precursors. This method can be extended to using other kinds of salt precursors to prepare a series of nanoporous metal oxides. The heating rate, calcination temperature and controlled particle size of the oxalate precursors are important factors to get well-defined pore structures. XRD, TG-DTA, TEM, SEM, XPS, wet chemical titration and N₂ sorption isotherm techniques are employed for morphology and structure characterizations. High surface area microporous manganese oxide (283 m² g⁻¹) and mesoporous nickel oxide (179 m² g⁻¹) with narrow pore distribution at around 1.0 nm and 6.0 nm, respectively, are obtained. Especially, we can tune the pore size of manganese oxides from microscope to mesoscope by controlling the thermal procedure. Electrochemical properties of manganese and nickel oxides are studied by cyclic voltammetry measurements in a mild aqueous electrolyte, which shows a high specific capacitance of 309 F g⁻¹ of microporous manganese oxide and a moderately high specific capacitance of 165 F g⁻¹ of mesoporous NiO due to their nanoporous structure, presenting the promising candidates for super capacitors (SC).

Composite scaffolds of mesoporous bioactive glass (MBG)/polycaprolactone (PCL) and conventional bioactive glass (BG)/PCL were fabricated by a solvent casting-particulate leaching method, and the structure and properties of the composite scaffolds were characterized. The measurements of the water contact angles suggest that the incorporation of either MBG or BG into PCL can improve the hydrophilicity of the composites, and the former is more effective than the later. The bioactivity of the composite scaffold is evaluated by soaking the scaffolds in a simulated body fluid (SBF) and the results show that the MBG/PCL composite scaffolds can induce a dense and continuous layer of apatite after soaking in SBF for 3 weeks, as compared with the scattered and discrete apatite particles on the BG/PCL composite scaffolds. Such improvements (improvements of the hydrophilicity and apatite forming ability) should be helpful for the extensive applications of PCL scaffold in tissue engineering. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008