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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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Structure of CH-CA-Spe nanogel. Schemes of chemical structure (a) and self-assembly (b) of CH-CA-Spe nanogel are shown.
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fig01: Structure of CH-CA-Spe nanogel. Schemes of chemical structure (a) and self-assembly (b) of CH-CA-Spe nanogel are shown.

Mentions: Among the various types of nanogel that we investigated, CH-CA-Spe nanogel was used as a new siRNA carrier. CH-CA-Spe formed polymer nanoparticles in 3-D networks, composed of physical cross-linking of polymer chains (Fig. 1a,b).(7,8) Cycloamylose (CA), which is produced by an enzymatic reaction between linear amylose and disproportionating enzymes, is a unique cyclic α-1,4-glucose polymer consisting of more than 100 glucose units.(9) CA can form inclusion complexes with a variety of hydrophobic drugs.(10) Destabilization of the endosomal membrane is essential to increase the transfection efficiency of non-viral nucleic acid delivery systems. Cycloamylose with spermine group acts as an effective plasmid DNA delivery carrier because CA can interact with endosomal membrane components, such as phospholipids or cholesterol, by forming a supramolecular complex, causing membrane instability.(7) Although CA has high potential as a new polysaccharide-based biomaterial, its biomedical application has thus far been limited.


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)

Structure of CH-CA-Spe nanogel. Schemes of chemical structure (a) and self-assembly (b) of CH-CA-Spe nanogel are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig01: Structure of CH-CA-Spe nanogel. Schemes of chemical structure (a) and self-assembly (b) of CH-CA-Spe nanogel are shown.
Mentions: Among the various types of nanogel that we investigated, CH-CA-Spe nanogel was used as a new siRNA carrier. CH-CA-Spe formed polymer nanoparticles in 3-D networks, composed of physical cross-linking of polymer chains (Fig. 1a,b).(7,8) Cycloamylose (CA), which is produced by an enzymatic reaction between linear amylose and disproportionating enzymes, is a unique cyclic α-1,4-glucose polymer consisting of more than 100 glucose units.(9) CA can form inclusion complexes with a variety of hydrophobic drugs.(10) Destabilization of the endosomal membrane is essential to increase the transfection efficiency of non-viral nucleic acid delivery systems. Cycloamylose with spermine group acts as an effective plasmid DNA delivery carrier because CA can interact with endosomal membrane components, such as phospholipids or cholesterol, by forming a supramolecular complex, causing membrane instability.(7) Although CA has high potential as a new polysaccharide-based biomaterial, its biomedical application has thus far been limited.

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