Younsoo Bae
University of Tokyo
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Publication
Featured researches published by Younsoo Bae.
Proceedings of the National Academy of Sciences of the United States of America | 2007
Mitsunobu R. Kano; Younsoo Bae; Caname Iwata; Yasuyuki Morishita; Masakazu Yashiro; Masako Oka; Tomoko Fujii; Akiyoshi Komuro; Kunihiko Kiyono; Michio Kaminishi; Kosei Hirakawa; Yasuyoshi Ouchi; Nobuhiro Nishiyama; Kazunori Kataoka; Kohei Miyazono
Transforming growth factor (TGF)-β plays a pivotal role in regulation of progression of cancer through effects on tumor microenvironment as well as on cancer cells. TGF-β inhibitors have recently been shown to prevent the growth and metastasis of certain cancers. However, there may be adverse effects caused by TGF-β signaling inhibition, including the induction of cancers by the repression of TGF-β-mediated growth inhibition. Here, we present an application of a short-acting, small-molecule TGF-β type I receptor (TβR-I) inhibitor at a low dose in treating several experimental intractable solid tumors, including pancreatic adenocarcinoma and diffuse-type gastric cancer, characterized by hypovascularity and thick fibrosis in tumor microenvironments. Low-dose TβR-I inhibitor altered neither TGF-β signaling in cancer cells nor the amount of fibrotic components. However, it decreased pericyte coverage of the endothelium without reducing endothelial area specifically in tumor neovasculature and promoted accumulation of macromolecules, including anticancer nanocarriers, in the tumors. Compared with the absence of TβR-I inhibitor, anticancer nanocarriers exhibited potent growth-inhibitory effects on these cancers in the presence of TβR-I inhibitor. The use of TβR-I inhibitor combined with nanocarriers may thus be of significant clinical and practical importance in treating intractable solid cancers.
Drug Discovery Today: Technologies | 2005
Nobuhiro Nishiyama; Younsoo Bae; Kanjiro Miyata; Shigeto Fukushima; Kazunori Kataoka
Polymeric micelles, supramolecular assemblies of block copolymers, are useful nanocarriers for the systemic delivery of drugs and genes. Recently, novel polymeric micelles with smart functions, such as targetability and stimuli-sensitivity, have emerged as promising carriers that enhance the efficacy of drugs and genes with minimal side effects. This review focuses on the construction and characteristic behaviors of intracellular environment-sensitive micelles that selectively exert drug activity and gene expression in live cells.:
ChemMedChem | 2007
May P. Xiong; Younsoo Bae; Shigeto Fukushima; M. Laird Forrest; Nobuhiro Nishiyama; Kazunori Kataoka; Glen S. Kwon
In gene therapy, the cytotoxicity of many polycations is undesirable and has been attributed to nonspecific membrane destabilizing effects and intracellular polyplex‐mediated toxicity. To help prolong the pharmacokinetic profile of nonviral vehicles for gene delivery, the cationic surface charge of current systems is typically shielded through the conjugation of polyethylene glycol (PEG) chains to the particle surface. However, the design of an intelligent polycation with environment‐sensing charge modulations is essential to minimize cytotoxicity and enhance gene expression. We have designed a novel di‐cationic block copolymer, poly(aspartate‐hydrazide)‐block‐poly(L‐lysine), capable of pH‐mediated endosomal membrane disruption based on charge interactions, which has negligible toxicity elsewhere to the cell. The poly(L‐lysine) segment, with a high pKa value of ∼9.4, preferentially forms a poly‐ion complex with the negative phosphate groups of pDNA, whereas the pH‐responsive poly(aspartate‐hydrazide) segment, with the comparatively lower pKa ∼5.0, is characterized by a substantial fraction of unprotonated amino groups at physiological pH. As a consequence, complexation between such a polymer and pDNA leads to the formation of a two‐layered nanoparticle. In particular, the nanoparticle possesses an unprotonated pH‐responsive segment to serve as both a scaffold for acid‐labile linkages of various moieties such as aldehyde‐PEG and to transition from neutral to charged for disrupting endosomal membranes, and safely enhancing gene expression. Our system supports an endosomal escape mechanism based on charge interactions rather than the proton‐sponge effect, and may be an important step towards engineering new classes of intelligent nonviral vectors.
Angewandte Chemie | 2003
Younsoo Bae; Shigeto Fukushima; Atsushi Harada; Kazunori Kataoka
Bioconjugate Chemistry | 2005
Younsoo Bae; Nobuhiro Nishiyama; Shigeto Fukushima; Hiroyuki Koyama; Matsumura Yasuhiro; Kazunori Kataoka
Molecular BioSystems | 2005
Younsoo Bae; Woo Dong Jang; Nobuhiro Nishiyama; Shigeto Fukushima; Kazunori Kataoka
Journal of the American Chemical Society | 2007
Yan Lee; Shigeto Fukushima; Younsoo Bae; Shigehiro Hiki; Takehiko Ishii; Kazunori Kataoka
Bioconjugate Chemistry | 2007
Younsoo Bae; Nobuhiro Nishiyama; Kazunori Kataoka
Journal of Controlled Release | 2007
Muri Han; Younsoo Bae; Nobuhiro Nishiyama; Kanjiro Miyata; Makoto Oba; Kazunori Kataoka
Journal of Controlled Release | 2006
Younsoo Bae; Kazunori Kataoka