A folic acid conjugated silica-titania porous hollow nanosphere for improved topical photodynamic therapy.

The folic acid conjugated hollow nanosphere is used to encapsulate protoporphyrin IX and is utilized for photodynamic therapy. This system represents a 3.33 times higher photodynamic efficiency than previous protoporphyrin IX-based systems. The result proposes a new opportunity for effective photodynamic therapy of folate receptor positive tumor cells.

Fabrication of barium- and strontium-doped silica/titania hollow nanoparticles and their synergetic effects on promoting neuronal differentiation by activating ERK and p38 pathways.

Pristine, barium-doped, and strontium-doped hollow nanoparticles (p-HNPs, Ba-HNP, and Sr-HNP; HNPs) are prepared by sonication-mediated etching and redeposition (SMER) method and alkali-earth-metal hydroxide solution treatment. The HNPs are investigated to facilitate synergetic neuronal differentiation through alkali-earth-metal doping and in conjunction with nerve growth factor (NGF). PC12 cells are used as model cells for neuronal differentiation. The differentiation efficiency is improved in the presence of the HNPs+NGF, and the neurite length is in the order of Sr-HNP+NGF > Ba-HNP+NGF > p-HNP+NGF > NGF. Silica/titania have increasing effect on both differentiation efficiency and neurite length, and doped barium/strontium influences additional elongation of the average neurite length. Take advantage of hollow structure, NGF is encapsulated into HNPs, and they are further applied for directly inducing differentiation. The maximum differentiation efficiency is 67% in presence of the NGF-encapsulated Sr-HNP, which was 1.3 times higher than previous research. Furthermore, the neurite length is also 2.7 times higher than MnO2 decorated poly(3,4-ethylenedioxythiophene) nanoellipsoids. Ba- and Sr-HNP may offer a possibility for novel application of metal-hybrid nanomaterials for cell differentiation, and can be expanded to other cellular applications.

Inkjet-printed polyaniline patterns for exocytosed molecule detection from live cells.

Polyaniline (PANi) patterns on flexible substrate are fabricated for biomolecule detection from live cells. PANi patterns are prepared by inkjet printing on polyethylene terephthalate film. Subsequently, arginine-glycine-aspartate (RGD) peptide is immobilized on the PANi pattern to selectively adhere cells. Rat pheochromocytoma PC12 cells are cultured on the RGD-immobilized PANi pattern, and patterned with high selectivity and growth. Additionally, the cells show focal adhesion on the RGD-immobilized PANi pattern, which are confirmed with vinculin staining and scanning electron microscopic images. To monitor dynamic biomolecular release from PC12 cells, RGD-immobilized PANi pattern is used for a real-time electrical signal detector. RGD-immobilized PANi patterning and sensing system represents outstanding ability to translate and amplify exocytosis molecules into a detectable signal as a transducer.

Screen-printed fluorescent sensors for rapid and sensitive anthrax biomarker detection.

Since the 2001 anthrax attacks, efforts have focused on the development of an anthrax detector with rapid response and high selectivity and sensitivity. Here, we demonstrate a fluorescence sensor for detecting anthrax biomarker with high sensitivity and selectivity using a screen-printing method. A lanthanide-ethylenediamine tetraacetic acid complex was printed on a flexible polyethersulfone film. Screen-printing deposition of fluorescent detecting moieties produced fluorescent patterns that acted as a visual alarm against anthrax.

Fluorescent polymer nanoparticle for selective sensing of intracellular hydrogen peroxide.

Fluorescent boronate-modified polyacrylonitrile (BPAN) nanoparticles of 50 nm diameter were fabricated for use as a selective H(2)O(2) sensor. The fluorescence intensity changed and an emission peak shifted when BPAN nanoparticles selectively interacted with H(2)O(2), relative to other reactive oxygen species (ROS). The BPAN nanoparticles undergo photoinduced electron transfer (PET) between a Schiff base moiety and boronate, which enhances the fluorescence and makes the nanoparticles suitable for selective ROS recognition. We demonstrate the use of these nanoparticles as a detector of endogenous H(2)O(2) produced in living cells. The representative features of the fluorescent BPAN nanoparticles that make them particularly attractive for H(2)O(2) and ROS detection are the following: they are easily synthesized as PET sensors; they exhibit a characteristic emission peak and peak shift that distinguishes reaction with H(2)O(2) from other ROS; and compared to organic compounds, the sensing moiety on BPAN polymer nanoparticles is more thermally stable and has superior mechanical properties, enabling their use in various biomedical applications.

Spatially controlled carbon sponge for targeting internalized radioactive materials in human body.

Carbon sponge, an adsorbent with spatially controlled structure is demonstrated for targeting internalized radiocesium and other radionuclides in human body. Three dimensionally ordered macroporous (3DOM) carbons derived from inverse opal replicas of colloidal-crystal template exhibit large surface area and high porosity, resulting in highly efficient adsorbents for radionuclides. It is also possible to enhance binding affinity and selectivity to radionuclide targets by decoration of 3DOM carbon surfaces with Prussian blue (PB) nanoparticles, and synthesized PB nanoparticles reveal low toxicity toward macrophage cells with potential advantages over oral administration. It is noteworthy that the maximum (133)Cs adsorption capacity of PB-decorated 3DOM carbons is 40.07 mmol g(-1) which is ca. 30 and 200 times higher than that of commercialized medicine Radiogardase(®) and bulk PB, respectively. Further, adsorption kinetics study indicates that the PB-decorated 3DOM carbons have the homogenous surface for (133)Cs ion adsorption and all sites have equal adsorption energies in terms of ion exchange between the cyano groups of the PB-decorated 3DOM carbons and radionuclides. As a concept of the oral-administrable "carbon sponge", the PB-decorated 3DOM carbons offer useful implications in the separation science of radioactive materials and important insight for designing novel materials for treatment of patients or suspected internal contamination with radioactive materials.

Efficient intracellular delivery of camptothecin by silica/titania hollow nanoparticles.

Silica/titania hollow nanoparticles (HNPs) with 50 nm were fabricated by using the dissolution and redeposition method and modified with anti-[human epidermal growth factor receptor 2] monoclonal antibody (herceptin), and their application as camptothecin (CPT) delivery agents to human breast cancer SK-BR-3 cells was investigated. Although the diameter of herceptin-modified HNPs (HER-HNP) is smaller than that of other reported mesoporous silica nanoparticles, the extensive hollow cavity of HNPs (ca. 30 nm) allowed the loading of a large amount of CPT. CPT-loaded HER-HNP (HER-HNP-CPT) did not release CPT in phosphate-buffered saline over a period of 24 h, however, HER-HNP-CPT in a hydrophobic solvent released its entire load of CPT. In addition, HER-HNPs were efficiently internalized owing to their herceptin conjugation and optimized size. To evaluate in vitro antitumor efficacy, apoptosis/necrosis and viability of HER-HNP-CPT-treated cells were investigated. When the cells were treated with HER-HNP-CPT for 30 min, a few apoptotic cells were observed. After 24 h, the viability of HER-HNP-CPT-treated SK-BR-3 decreased to 60 %, which revealed highly efficient chemotherapy. However, CPT loaded into HNP or HER-HNP had no significant effects on the viability of macrophages. Judging from these data, HER-HNPs are very suitable for application in anticancer therapy. A HER-HNP-CPT drug delivery system offers a new direction for a hydrophobic anticancer drug carrier and can be expanded to practical applications with further studies.

Fluorescent europium-modified polymer nanoparticles for rapid and sensitive anthrax sensors.

Novel fluorescent polyacrylonitrile nanoparticles were synthesized by microemulsion polymerization and Schiff base modification. By further modification with europium, the polyacrylonitrile nanoparticles could be used as a highly sensitive and rapid sensor for Bacillus anthracis spore detection in aqueous solution. The europium-modified polyacrylonitrile nanoparticles were readily combined with dipicolinic acid as a unique biomarker of B. anthracis, leading to high fluorescence emission. These nanoparticles enabled ratiometric detection without instrument-specific calibration due to the internal fluorescence reference. Additionally, the europium-modified polyacrylonitrile nanoparticle sensors exhibited a remarkable limit of detection (10pM) for dipicolinic acid and outstanding selectivity (160×) over aromatic ligands in aqueous solution. The ultrafine nanoparticle sensor showed a high capability for detecting anthrax due to the increased surface area-to-volume ratio and enhanced dispersibility.

Cellular uptake, cytotoxicity, and ROS generation with silica/conducting polymer core/shell nanospheres.

The cellular response to conducting polymer (CP) nanospheres with similar physical properties was evaluated by in vitro cellular uptake and cytotoxicity in mouse macrophage RAW 264.7 and rat pheochromocytoma PC-12 cells. Four different CPs (polythiophene, poly(3,4-ethylenedioxythiophene), polyaniline, and polypyrrole) were deposited onto silica nanoparticles with a diameter of ca. 22 nm. Cellular uptake of silica/CP core/shell nanospheres in both cell lines was observed by transmission electron microscopy and they were internalized via phagocytosis and endocytosis. Cytotoxic effects were systemically assessed using live-cell microscopy, viability, oxidative stress, and lactate dehydrogenase assays. Silica/polythiophene core/shell nanospheres were the most toxic in both cell lines examined, because of the cellular effects of sulfur atoms. On the other hand, silica/polypyrrole core/shell nanospheres caused the lowest levels of toxicity in both cell lines. Furthermore, both rat and mouse cell viability was concentration-dependent with the nanospheres. These findings enhance nanotoxicological information regarding CP nanospheres when used with macrophage and neuronal cells, which may be useful in their application in bioelectronic and biomedical fields.

Shape-dependent cytotoxicity of polyaniline nanomaterials in human fibroblast cells.

The toxicity of polyaniline (PANI) nanomaterials with four different aspect ratios on human lung fibroblast cells was investigated by cell viability assay, cytotoxicity assay, apoptosis/necrosis measurement, and reactive oxygen species production. The toxicity increased with decreasing aspect ratio of PANI nanomaterials. In contrast, the highest aspect ratio PANI nanomaterials showed similar results with bulk PANI materials. The adverse effect of PANI nanomaterials was also concentration- and time-dependent. Low aspect ratio PANI nanomaterials induced more necrosis and more reactive oxygen species than others. These results provide new understanding of shape-dependent toxicity of nanomaterials.

Cytotoxicity of, and innate immune response to, size-controlled polypyrrole nanoparticles in mammalian cells.

Monodisperse polypyrrole (PPy) nanoparticles with five different diameters (20, 40, 60, 80, and 100 nm) were fabricated via chemical oxidation polymerization in order to evaluate size-dependent cytotoxicity. The cellular uptake of PPy nanoparticles in human lung fibroblasts (IMR90) and mouse alveolar macrophages (J774A.1) was observed by transmission electron microscopy. The nanoparticles were internalized into the IMR90 via endocytosis. In the J774A.1, the nanoparticles were entered via phagocytosis and endocytosis. Endocytosed nanoparticles were transported to lysosome via endosome-network. The cytotoxicity and innate immune response of PPy-treated cells were systematically investigated by viability assay, oxidative stress, apoptosis/necrosis, and expression of costimulatory molecules. The viability, oxidative stress, and apoptosis/necrosis of PPy-treated cells revealed size- and dose-dependency. Because of phagocytosis, PPy treatment had more adverse effects on the J774A.1 than the IMR90. Innate immune response of PPy-treated macrophages was measured by the expression of costimulatory molecules on surface of the cells. The expression of costimulatory molecules involved in Th1 response (CD40 and CD80) was lightly up-regulated and the other costimulatory molecule related in Th2 response (CD86) was less expressed than a negative control. These findings may provide better nanotoxicological information of polymer nanomaterials, and support the further development of PPy nanoparticles in bioelectronic applications.

Cellular uptake, cytotoxicity, and innate immune response of silica-titania hollow nanoparticles based on size and surface functionality.

Silica-titania hollow nanoparticles (HNPs) with uniform diameters of 25, 50, 75, 100, and 125 nm were fabricated by dissolution and redeposition method in order to evaluate size dependent cellular response. Surface-modified HNPs with cationic, anionic, and neutral functional group were prepared by silane treatment. We systematically investigated cellular internalization, toxicity, and innate immune response of HNPs in human breast cancer (SK-BR-3) and mouse alveolar macrophage (J774A.1) cells. Size- and surface functionality-dependent cellular uptake of HNPs was investigated by fluorescence labeling (fluorescein isothiocyanate), inductively coupled plasma-emission spectroscopy, and ultrastructural resolution using transmission electron microscopy. Viability, reactive oxygen species, and apoptosis/necrosis of HNP-treated J774A.1 revealed the size-dependent phenomenon. Innate immune response of HNP-treated macrophages was measured by three cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor α. Among the HNPs of different sizes, 50-nm HNPs demonstrated the highest toxic influence on macrophages. Among the HNPs with surface functionalities, cationic HNPs demonstrated the most toxic effect on J774A.1 and the highest uptake efficiency. The toxicity results of HNP-treated macrophages were consistent with the cellular internalization efficiency. These findings provide size- and surface functionality-dependent nanotoxicity and uptake of HNPs, and lead to HNPs for bioapplications such as drug delivery and imaging probe.

Photoluminescent polymer nanoparticles for label-free cellular imaging.

Novel polymer based photoluminescent nanoparticles were fabricated by ultra-sound induced emulsion polymerization and applied to bioimaging of human breast cancer SK-BR-3 cells after ethylenediamine treatment and conjugation with anti-ErbB2 antibody.

Shape-dependent cytotoxicity and proinflammatory response of poly(3,4-ethylenedioxythiophene) nanomaterials.

Poly(3,4-ethylenedioxythiophene) (PEDT) is recognized as one of the most promising conducting polymers for future applications in the fields of electronics, optics, energy storage/conversion, and biomedical science. The toxicity of PEDT could be considered to affect the potential for its widespread application. Herein, the cytotoxicity and proinflammatory response of PEDT nanomaterials of three different shapes toward human lung fibroblast (IMR90) and mouse alveolar macrophage (J774A.1) cells are investigated. The shape-dependent toxicity of the PEDT nanomaterials is evaluated by examining cell morphological change, cytotoxicity, apoptosis/necrosis, oxidative stress, and immune response. The cytotoxicity and apoptosis of the nanomaterials increase with their decreasing aspect ratio in both cell lines. The formation of reactive oxygen species in cells treated with PEDT nanomaterials is dependent on the shape and concentration of the nanomaterial. Proinflammatory cytokines, such as interleukin-1, interleukin-6, and tumor necrosis factor alpha from macrophages, are induced by PEDT nanomaterial-treated cells.