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- W2025561680 abstract "atelocollagen, have been well studied in animal models. A common hurdle of systemic administration of these carriers is, however, accumulation in the reticuloendothelial system (RES), including liver and spleen. We here show a novel delivery system using super apatite ultra-nanoparticles (sApa), which are 5~30nm in diameter and consist of inorganic ions, such as Ca, Pi and CO 3 . The particles are highly stable at the physiological pH 7.4 and quickly degradable at the pH 5.5 in the endosomal compartments. So far we have demonstrated higher transfection efficiency of siRNA in colon cancer cells using sApa, compared with the lipofectamine 2000. Based on these in vitro data, we have conducted for the first time in vivo systemic administration of siRNA using pH-sensitive inorganic ultra-nanoparticles with a range of 5~30nm in diameter, to reveal their distribution in organs and anti-tumor efficacy. Material and Methods: BALB/cA nude mice were inoculated s.c. with human colon cancer cell HCT116 (1×106 cell) to prepare a solid tumor model. Biodistribution study of sApa incorporating fluorescently labelled siRNA (sApa-siRNA) was performed when the tumors reached 10mm in diameter. Fluorescent microscopic images of tissue sections such as liver, kidney, spleen, and the tumor exhibited the microdistribution of fluorescently labeled siRNA. A study on anti-tumor activity was performed when the tumors were 5~6mm in diameter. sApa incorporating 15 mg of siRNA against survivin was intravenously injected into the tail vein on days 0, 2, 4, 7, 9, 11, 14, 16, and day 18. Results: At 4h post systemic administration, we observed significantly higher fluorescence signals in tumor sections treated with sApa-siRNA (2.7±0.64-fold, mean±SE, normalized to samples treated with saline) than those with naked siRNA (0.95±0.20-fold, p < 0.01, n = 6). At both 4h and 12h, the sApa-siRNA exhibited 10-fold and 26-fold lower accumulation in liver, and 4-fold and 5-fold lower distribution in kidney, respectively (p < 0.05, n = 3). As for the anti-tumor activity, from day 11, tumor volume of the group treated with sApa-siRNA against survivin was significantly lower than those treated with sApa incorporating negative control siRNA or saline (p < 0.001, n = 10). Conclusions: A novel in vivo delivery system using pH-sensitive super apatite ultra-nanoparticles with 5~30nm in diameter can be characterized as tumor-specific accumulation and high antitumor efficacy. Our data suggest that sApa delivery system is of vital use to experimental approaches both in vitro and in vivo, and ultra-nanoparticles may open a new avenue in nanoparticle-based medicine." @default.
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- W2025561680 date "2012-11-01" @default.
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- W2025561680 title "112 Hyaluronic Acid Based Cisplatin Nanogel Selectively Inhibits Growth and Metastasis of Non-Small Cell Lung Cancer, Which Overexpresses CD44" @default.
- W2025561680 doi "https://doi.org/10.1016/s0959-8049(12)71910-x" @default.
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