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Cycloamylose-nanogel drug delivery system-mediated intratumor silencing of the vascular endothelial growth factor regulates neovascularization in tumor microenvironment.

Fujii H, Shin-Ya M, Takeda S, Hashimoto Y, Mukai SA, Sawada S, Adachi T, Akiyoshi K, Miki T, Mazda O - Cancer Sci. (2014)

Bottom Line: The siVEGF/nanogel complex was engulfed by renal cell carcinoma (RCC) cells through the endocytotic pathway, resulting in efficient knockdown of VEGF.Intra-tumor injections of the complex significantly suppressed neovascularization and growth of RCC in mice.The treatment also inhibited induction of myeloid-derived suppressor cells, while it decreased interleukin-17A production.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

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Related in: MedlinePlus

6-carboxyfluorescein (FAM)-labeled siRNA (FAM-siRNA)/CH-CA-Spe nanogel complex was endocytosed by tumor cells. Renca cells were transfected with 6-carboxyfluorescein (FAM)-labeled siRNA by means of CH-CA-Spe nanogel or cationic liposome. Three (a) and seven (b) hours later, lysosomes were stained with LysoTracker Blue DND-22 (Life Technologies) and visualized by confocal laser scanning microscopy. Scale bars represent 10 μm.
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fig03: 6-carboxyfluorescein (FAM)-labeled siRNA (FAM-siRNA)/CH-CA-Spe nanogel complex was endocytosed by tumor cells. Renca cells were transfected with 6-carboxyfluorescein (FAM)-labeled siRNA by means of CH-CA-Spe nanogel or cationic liposome. Three (a) and seven (b) hours later, lysosomes were stained with LysoTracker Blue DND-22 (Life Technologies) and visualized by confocal laser scanning microscopy. Scale bars represent 10 μm.

Mentions: Intracellular transport of the siRNA/nanogel complex was analyzed by confocal laser scanning microscopy. FAM (green fluorescence)-labeled siRNA was incorporated into CH-CA-Spe nanogel, and added to Renca cells. Lysosome was stained with LysoTracker (fluorescent blue) and observed at different time points. As shown in Figure 3a, FAM-siRNA was present on the surface of the cells 3 h after addition of the complex. Seven hours after the transfection, the FAM-siRNA was localized at the lysosomal compartment as demonstrated by a cyan fluorescence in the merged image (Fig. 3b).


Cycloamylose-nanogel drug delivery system-mediated intratumor silencing of the vascular endothelial growth factor regulates neovascularization in tumor microenvironment.

Fujii H, Shin-Ya M, Takeda S, Hashimoto Y, Mukai SA, Sawada S, Adachi T, Akiyoshi K, Miki T, Mazda O - Cancer Sci. (2014)

6-carboxyfluorescein (FAM)-labeled siRNA (FAM-siRNA)/CH-CA-Spe nanogel complex was endocytosed by tumor cells. Renca cells were transfected with 6-carboxyfluorescein (FAM)-labeled siRNA by means of CH-CA-Spe nanogel or cationic liposome. Three (a) and seven (b) hours later, lysosomes were stained with LysoTracker Blue DND-22 (Life Technologies) and visualized by confocal laser scanning microscopy. Scale bars represent 10 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317968&req=5

fig03: 6-carboxyfluorescein (FAM)-labeled siRNA (FAM-siRNA)/CH-CA-Spe nanogel complex was endocytosed by tumor cells. Renca cells were transfected with 6-carboxyfluorescein (FAM)-labeled siRNA by means of CH-CA-Spe nanogel or cationic liposome. Three (a) and seven (b) hours later, lysosomes were stained with LysoTracker Blue DND-22 (Life Technologies) and visualized by confocal laser scanning microscopy. Scale bars represent 10 μm.
Mentions: Intracellular transport of the siRNA/nanogel complex was analyzed by confocal laser scanning microscopy. FAM (green fluorescence)-labeled siRNA was incorporated into CH-CA-Spe nanogel, and added to Renca cells. Lysosome was stained with LysoTracker (fluorescent blue) and observed at different time points. As shown in Figure 3a, FAM-siRNA was present on the surface of the cells 3 h after addition of the complex. Seven hours after the transfection, the FAM-siRNA was localized at the lysosomal compartment as demonstrated by a cyan fluorescence in the merged image (Fig. 3b).

Bottom Line: The siVEGF/nanogel complex was engulfed by renal cell carcinoma (RCC) cells through the endocytotic pathway, resulting in efficient knockdown of VEGF.Intra-tumor injections of the complex significantly suppressed neovascularization and growth of RCC in mice.The treatment also inhibited induction of myeloid-derived suppressor cells, while it decreased interleukin-17A production.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Kyoto Prefectural University of Medicine, Kyoto, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Show MeSH
Related in: MedlinePlus