Inorganic-organic magnetic nanocomposites for use in preventive medicine: a rapid and reliable elimination system for cesium.

PURPOSE: To investigate the potential use of Prussian blue-coated magnetic nanoparticles, termed "Prussian blueberry", to bring about the magnetic elimination of cesium. METHODS: Prussian blueberry were prepared by a layer-by-layer assembly method. The morphology, structure and physical properties of the Prussian blueberry were investigated as was their ability to magnetically eliminate cesium. RESULTS: We confirmed that Prussian blueberry were composed of a magnetite nanoparticle-core and a Prussian blue-shell. Under a magnetic field, Prussian blueberry (5 mg) reduced the cesium concentration of seawater (3 ml) from 150 ppm to about 50 ppm; but regular Prussian blue could not magnetically eliminate cesium. Moreover, Prussian blueberry removed a similar proportion of cesium from a larger volume of seawater, and from fetal bovine serum and cow's milk. CONCLUSIONS: Under a magnetic field, Prussian blueberry was able to rapidly eliminate cesium from seawater and from biological matrices such as serum and milk.

Hybrid micro-particles as a magnetically-guidable decontaminant for cesium-eluted ash slurry.

Decontamination of the radioactive cesium that is widely dispersed owing to a nuclear power station accident and concentrated in fly ash requires an effective elimination system. Radioactive fly ash contains large amounts of water-soluble cesium that can cause severe secondary contamination and represents a serious health risk, yet its complete removal is complicated and difficult. Here it is shown that a new fine-powder formulation can be magnetically guided to eliminate cesium after being mixed with the ash slurry. This formulation, termed MagCE, consists of a ferromagnetic porous structure and alkaline- and salt-resistant nickel ferrocyanide. It has potent cesium-adsorption- and magnetic-separation-properties. Because of its resistance against physical and chemical attack such as with ash particles, as well as with the high pH and salt concentration of the ash slurry, MagCE simplifies the decontamination process without the need of the continued presence of the hazardous water-soluble cesium in the treated ash.

A novel magnetic crystal-lipid nanostructure for magnetically guided in vivo gene delivery.

Cancer gene therapy requires a safe and effective gene delivery system. Polymer- and lipid-coated magnetic nanocrystals have been used to deliver silencing RNA, but synthesizing these magnetic vectors is difficult. Here, we show that a new nanoparticle formulation can be magnetically guided to deliver and silence genes in cells and tumours in mice. This formulation, termed LipoMag, consists of an oleic acid-coated magnetic nanocrystal core and a cationic lipid shell. When compared with the commercially available PolyMag formulation, LipoMag displayed more efficient gene silencing in 9 of 13 cell lines, and better anti-tumour effects when systemically administered to mice bearing gastric tumours. By delivering an optimized sequence of a silencing RNA that targets the epidermal growth factor receptor of tumour vessels, the intended therapeutic benefit was achieved with no evident adverse immune reaction or untoward side effects.

Preclinical study of a "tailor-made" combination of NK4-expressing gene therapy and gefitinib (ZD1839, Iressa) for disseminated peritoneal scirrhous gastric cancer.

We evaluated the effect of a "tailor-made" chemo-gene therapy in scirrhous gastric cancer (SGC)-bearing nude mice. For this tailor-made approach, we first selected gefitinib (epidermal growth factor receptor-tyrosine kinase inhibitor)-sensitive SGC cell lines, and 5/8 cell lines demonstrated various degrees of gefitinib-sensitivity. In the highly gefitinib-sensitive NUGC-4, the biological response to NK4 (HGF antagonist/angiogenesis inhibitor) was examined. Subsequently, the composition of an NK4-expressing ternary complex (cationic lipid/nucleic acid/HMG-1, 2 protein) was optimized for maximum transfection activity in NUGC-4. Finally, mice were peritoneally coinoculated with NUGC-4 and scirrhous-associated gastric fibroblasts, NF22, on day 0. Animal models were orally administrated gefitinib (50 mg/kg/day, on days 7-28), and peritoneally NK4-expressing ternary complex (on days 14, 21 and 28). NK4-expression suppressed the gefitinib-resistance induced by the interaction between fibroblasts and SGC, and eventually, this tailor-made combination synergistically decelerated the disease progression by inhibiting proliferative, angiogenic and antiapoptotic effects in tumor tissues. On day 28, both the hemoglobin concentration (g/dl) (control (n = 8), 11.9; treated (n = 8), 17.3; p = 0.0014) and the numbers of mice in good condition (control, 2; treated, 8; p = 0.0012) were significantly greater, and the abdominal girth (mm) (control, 81.1; treated, 70.3; p = 0.0036) was significantly reduced. The median points of bloody ascite-free survival time (days) (control, 22; treated, 44; p < 0.0001) and time to euthanasia (days) (control, 36.5; treated, 56; p < 0.0001) were also significantly prolonged. This combination is a potentially useful approach to the treatment of peritoneal gefitinib-sensitive SGC dissemination.

Enhanced photodynamic antitumor effect on gastric cancer by a novel photosensitive stealth liposome.

Lipophilic photosensitizers hold potential for cancer photodynamic therapy. We sought to develop a novel photosensitive stealth liposome (PSSL) which incorporating a lipophilic photosensitizer into its lipid bilayer and to examine its photoactivity. We prepared PSSL composed of lipophilic chlorin e6 (Ce6) ester, dilauroylphosphatidylcholine, dioleoylphosphatidylethanolamine and distearoyl-phosphoethanolamine-N-[poly (ethylene glycol) 2000] and evaluated its photodynamic effect against gastric cancer cell lines and tumor-bearing nude mice models. In gastric cancer cell lines, LC(80) of PSSL was a maximum of 53 times as low as that of Ce6 sodium salt (Ce6-Na). PSSL completely destroyed all tumors in animal models and tumor recurrence levels were minimal (1.5 +/- 0.9%). PSSL achieved greater photodynamic effects in gastric cancer cell lines and in murine models than Ce6-Na. PSSL holds promise for photodynamic therapy for gastric cancer.