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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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CH-CA-Spe nanogel enabled effective intratumor siRNA delivery and silencing of vascular endothelial growth factor (VEGF). Tumor-bearing mice were injected with FITC-siRNA alone, FITC-siRNA/cationic liposome complex and FITC-siRNA/nanogel complex into preestablished subcutaneous renal cell carcinoma (RCC) tumors (20 μg of siRNA/50 μL/tumor). Three (a) and twenty-four (b) hours later, the tumor tissue was observed under confocal laser scanning microscopy. Representative bright field (left), fluorescent (middle) and merged (right) images are shown. Scale bar, 100 μm. (c) Tumor-bearing mice were given an intratumoral injection with siRNA/nanogel complex (20 μg of siRNA/50 μL/tumor) or drug delivery system alone, as indicated. Twenty-four hours later, VEGF mRNA levels were measured by real-time RT-PCR. Data represent the means ± SD (n = 5–7).*P < 0.05 versus control non-silencing siRNA (siCont) or cationic liposome group.
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fig04: CH-CA-Spe nanogel enabled effective intratumor siRNA delivery and silencing of vascular endothelial growth factor (VEGF). Tumor-bearing mice were injected with FITC-siRNA alone, FITC-siRNA/cationic liposome complex and FITC-siRNA/nanogel complex into preestablished subcutaneous renal cell carcinoma (RCC) tumors (20 μg of siRNA/50 μL/tumor). Three (a) and twenty-four (b) hours later, the tumor tissue was observed under confocal laser scanning microscopy. Representative bright field (left), fluorescent (middle) and merged (right) images are shown. Scale bar, 100 μm. (c) Tumor-bearing mice were given an intratumoral injection with siRNA/nanogel complex (20 μg of siRNA/50 μL/tumor) or drug delivery system alone, as indicated. Twenty-four hours later, VEGF mRNA levels were measured by real-time RT-PCR. Data represent the means ± SD (n = 5–7).*P < 0.05 versus control non-silencing siRNA (siCont) or cationic liposome group.

Mentions: Successively, to assess in vivo localization and stability of the siRNA that was delivered into tumors by CH-CA-Spe nanogel, we injected FITC-labeled siRNA alone or in combination with cationic liposome or nanogel into pre-established RCC tumors in mice. In the tumors that received FITC-siRNA alone, we could detect an extremely sparse distribution of signals, while a sparse signal was scattered in the tumor tissues of the FITC-siRNA/cationic liposome complex. In sharp contrast, we could confirm greater fluorescence signals widely distributed in the FITC-siRNA/nanogel-injected tumors (Fig. 4a). Twenty-four hours after the injection, the FITC signal was clearly observed only in this group (Fig. 4b). Therefore, it appears that siRNA delivered by means of the CH-CA-Spe nanogelis stably maintained in tumor tissue.


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)

CH-CA-Spe nanogel enabled effective intratumor siRNA delivery and silencing of vascular endothelial growth factor (VEGF). Tumor-bearing mice were injected with FITC-siRNA alone, FITC-siRNA/cationic liposome complex and FITC-siRNA/nanogel complex into preestablished subcutaneous renal cell carcinoma (RCC) tumors (20 μg of siRNA/50 μL/tumor). Three (a) and twenty-four (b) hours later, the tumor tissue was observed under confocal laser scanning microscopy. Representative bright field (left), fluorescent (middle) and merged (right) images are shown. Scale bar, 100 μm. (c) Tumor-bearing mice were given an intratumoral injection with siRNA/nanogel complex (20 μg of siRNA/50 μL/tumor) or drug delivery system alone, as indicated. Twenty-four hours later, VEGF mRNA levels were measured by real-time RT-PCR. Data represent the means ± SD (n = 5–7).*P < 0.05 versus control non-silencing siRNA (siCont) or cationic liposome group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig04: CH-CA-Spe nanogel enabled effective intratumor siRNA delivery and silencing of vascular endothelial growth factor (VEGF). Tumor-bearing mice were injected with FITC-siRNA alone, FITC-siRNA/cationic liposome complex and FITC-siRNA/nanogel complex into preestablished subcutaneous renal cell carcinoma (RCC) tumors (20 μg of siRNA/50 μL/tumor). Three (a) and twenty-four (b) hours later, the tumor tissue was observed under confocal laser scanning microscopy. Representative bright field (left), fluorescent (middle) and merged (right) images are shown. Scale bar, 100 μm. (c) Tumor-bearing mice were given an intratumoral injection with siRNA/nanogel complex (20 μg of siRNA/50 μL/tumor) or drug delivery system alone, as indicated. Twenty-four hours later, VEGF mRNA levels were measured by real-time RT-PCR. Data represent the means ± SD (n = 5–7).*P < 0.05 versus control non-silencing siRNA (siCont) or cationic liposome group.
Mentions: Successively, to assess in vivo localization and stability of the siRNA that was delivered into tumors by CH-CA-Spe nanogel, we injected FITC-labeled siRNA alone or in combination with cationic liposome or nanogel into pre-established RCC tumors in mice. In the tumors that received FITC-siRNA alone, we could detect an extremely sparse distribution of signals, while a sparse signal was scattered in the tumor tissues of the FITC-siRNA/cationic liposome complex. In sharp contrast, we could confirm greater fluorescence signals widely distributed in the FITC-siRNA/nanogel-injected tumors (Fig. 4a). Twenty-four hours after the injection, the FITC signal was clearly observed only in this group (Fig. 4b). Therefore, it appears that siRNA delivered by means of the CH-CA-Spe nanogelis stably maintained in tumor tissue.

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