Member

Research Theme

1. Regulation of cell functions by dynamic surfaces
   Cyclic molecules threaded in polyrotaxanes are known to move and rotate along a polymer axle. Focusing on the mobility of the cyclic molecules in polyrotaxanes, our group has designed biomaterials surfaces with dynamic properties by utilizing a molecularly movable architecture of polyrotaxanes and examined their effects on a variety of interactions with biological components, such as proteins and cells. Interestingly, dynamic surfaces directs the differentiation of stem cells.
2. Therapeutic applications of biocleavable polyrotaxanes for metabolic diseases
   Biocleavable polyrotaxanes that can release threaded β-cyclodextrins (β?CDs) under cellular environments have been developed as a therapeutic agent for various intractable diseases. The intracellular release of β?CDs from the polytrotaxanes interacts with the intracellular lipids and cholesterol to modulate the cellular metabolic functions. Our group has found that the polyrotaxanes showed significant therapeutic effects in a mouse model of Niemann-Pick type C diseases, which is a rare metabolic disorder and cholesterols are accumulated in lysosomes.
3. Nanomedicine applications of biomolecules by complexation with polyrotaxanes
   Biopharmaceutical agents, such as nucleic acids and proteins, have recently attracted much attention as a new class of drug. To enhance stability and biological activities of the biopharmaceutical agents, the supramolecular polyelectrolyte complexes with polyrotaxanes have been designed, and their therapeutic efficacies have been evaluated in vitro and in vivo.
4. Design of smart dental materials based on biocleavable polyrotaxanes
   In the current dental treatment, a variety of photocurable resins are used, such as in composite resins and dental adhesives. However, these conventional resins and adhesives are difficult to remove after polymerization. Our group has developed photo-labile polyrotaxanes that can dissociate by the UV-light irradiation and investigated the application of the photo-labile polyrotaxanes as a component of dental adhesive for orthodontics. By the use of this polyrotaxanes, the orthodontic brackets will be able to remove by simple light irradiation.

Publications

2018

1. T. Kanemaru, Y. Ohyama, K. Aoki, A. Tamura, N. Yui, S. Yamaguchi, Y. Mochida.Modulation of matrix mineralization by von Willebrand factor C domain containing 2 in vivo and in vitro. J. Oral Tissue Eng. 15 (3), 131-142 (2018).
2. K. Nishida, A. Tamura, N. Yui. ER stress-mediated autophagic cell death induction through methylated β-cyclodextrins-threaded acid-labile polyrotaxanes. J. Control. Release 275, 20-31 (2018).
3. T. Inada, A. Tamura, M. Terauchi, S. Yamaguchi, N. Yui. A silencing-mediated enhancement of osteogenic differentiation by supramolecular ternary siRNA polyplexes comprising biocleavable cationic polyrotaxanes and anionic fusogenic peptides. Biomater. Sci. 6 (2), 440-450 (2018).
4. A. Tamura, N. Yui. Polyrotaxane-based systemic delivery of β-cyclodextrins for potentiating therapeutic efficacy in a mouse model of Niemann-Pick type C disease. J. Control. Release 269, 148-158 (2018).



2017

5. A. Tamura, M. Ohashi, K. Nishida, N. Yui. Acid-induced intracellular dissociation of β-cyclodextrin-threaded polyrotaxanes directed towards attenuating phototoxicity of bisretinoids through promoting excretion. Mol. Pharm. 14 (12), 4714-4724 (2017).
6. A. Tamura, M. Ohashi, N. Yui. Oligo(ethylene glycol)-modified β-cyclodextrin-based polyrotaxanes for simultaneously modulating solubility and cellular internalization efficiency. J. Biomater. Sci., Polym. Ed. 28 (10-12), 1124-1139 (2017).
7. Y. Arisaka, N. Yui. Tethered bone morphogenetic protein-2 onto sulfonated-polyrotaxane based surfaces promotes osteogenic differentiation of MC3T3-E1 cells. J. Biomater. Sci., Polym. Ed. 28 (10-12), 974-985 (2017).
8. M. Terauchi, T. Inada, T. Kanemaru, G. Ikeda, A. Tonegawa, K. Nishida, Y. Arisaka, A. Tamura, S. Yamaguchi, N. Yui. Potentiating bioactivity of BMP-2 by polyelectrolyte complexation with sulfonated polyrotaxanes to induce rapid bone regeneration in a mouse calvarial defect. J. Biomed. Mater. Res. Part A 105 (5), 1355-1363 (2017).



2016

9. A. Tamura, A. Tonegawa, Y. Arisaka, N. Yui. Versatile synthesis of end-reactive polyrotaxanes applicable to fabrication of supramolecular biomaterials. Beilstein J. Org. Chem. 12 (1), 2883-2892 (2016).
10. M. Terauchi, T. Inada, A. Tonegawa, A. Tamura, S. Yamaguchi, K. Harada, N. Yui. Supramolecular inclusion complexation of simvastatin with methylated β-cyclodextrins for promoting osteogenic differentiation. Int. J. Biol. Macromol. 93 Part B, 1492-1498 (2016).
11. K. Nishida, A. Tamura, N. Yui. Tailoring the temperature-induced phase transition and coacervate formation of methylated β-cyclodextrins-threaded polyrotaxanes in aqueous solution. Macromolecules 49 (16), 6021-6030 (2016).
12. A. Tamura, K. Nishida, N. Yui. Lysosomal pH-inducible supramolecular dissociation of polyrotaxanes possessing acid-labile N-triphenylmethyl end groups and their therapeutic potential for Niemann-Pick type C disease. Sci. Technolo. Adv. Mater. 17 (1), 361-374 (2016).
13. J.-H. Seo, M. Hirata, S. Kakinoki, T. Yamaoka, N. Yui. Dynamic polyrotaxane-coated surface for effective differentiation of mouse induced pluripotent stem cells into cardiomyocytes. RSC Adv. 6 (42), 35668-35676 (2016).



2015

14. A. Ge, J.-H. Seo, L. Qiao, N. Yui, S. Ye. Structural reorganization and fibrinogen adsorption behaviors on the polyrotaxane surfaces investigated by sum frequency generation spectroscopy. ACS Appl. Mater. Interfaces 7 (40), 22709-22718 (2015).
15. J.-H. Seo, M. Fushimi, N. Matsui, T. Takagaki, J. Tagami, N. Yui. UV-Cleavable polyrotaxane cross-linker for modulating mechanical strength of photocurable resin plastics. ACS Macro Lett. 4 (10), 1154-1157 (2015).
16. A. Tamura, G. Ikeda, K. Nishida, N. Yui. Cationic polyrotaxanes as a feasible framework for the intracellular delivery and sustainable activity of anionic enzymes: a comparison study with methacrylate-based polycations. Macromol. Biosci. 15 (8), 1134-1145 (2015).
17. M. Terauchi, G. Ikeda, K. Nishida, A. Tamura, S. Yamaguchi, K. Harada, N. Yui. Supramolecular polyelectrolyte complexes of bone morphogenetic protein-2 with sulfonated polyrotaxanes to induce enhanced osteogenic differentiation. Macromol. Biosci. 15 (7), 953-964 (2015).
18. S. Yamada, Y. Sanada, A. Tamura, N. Yui, K. Sakurai. Chain architecture and flexibility of α-cyclodextrin/PEG polyrotaxanes in dilute solutions. Polym. J. 47 (6), 464-467 (2015).
19. K. Nishida, A. Tamura, N. Yui. Acid-labile polyrotaxane exerting endolysosomal pH-sensitive supramolecular dissociation for therapeutic applications. Polym. Chem. 6 (21), 4040-4047 (2015).
20. A. Tamura, N. Yui. β-Cyclodextrin-threaded biocleavable polyrotaxanes ameliorate impaired autophagic flux in Niemann-Pick type C disease. J. Biol. Chem. 290 (15), 9442-9454 (2015).
21. A. Tamura, I. Fukumoto, N. Yui, M. Matsumura, H. Miura. Increasing the repeating units of ethylene glycol-based dimethacrylates directed towards reduced oxidative stress and co-stimulatory factors expression in human monocytic cells. J. Biomed. Mater. Res. Part A 103 (3), 1060-1066 (2015).
22. J.-H. Seo, Y. Tsutsumi, A. Kobari, M. Shimojo, T. Hanawa, N. Yui. Modulating friction behavior in water by changing the combination of the loop- and graft-type poly(ethylene glycol) surfaces. Soft Matter 11 (5), 936-942 (2015).
23. J.-H. Seo, S. Kakinoki, T. Yamaoka, N. Yui. Directing stem cell differentiation by changing the molecular mobility of supramolecular surfaces. Adv. Healthcare Mater. 4 (2), 215-222 (2015).
24. S. Kakinoki, J.-H. Seo, Y. Inoue, K. Ishihara, N. Yui, T. Yamaoka. Mobility of the Arg-Gly-Asp (RGD) ligand on the outermost surface of biomaterials suppresses integrin-mediated mechanotransduction and subsequent cell functions. Acta Biomater. 13, 42-51 (2015).



2014

25. J.-H. Seo, S. Nakagawa, K. Hirata, N. Yui. Synthesis of a resin monomer-soluble polyrotaxane crosslinker containing cleavable end groups. Beilstein J. Org. Chem. 10, 2623-2629 (2014).
26. K. Nam, J.-H. Seo, T. Kimura, N. Yui, A. Kishida. Relationship between molecular mobility, fibrillogenesis of collagen molecules, and inflammatory response: an experimental study in vitro and in vivo. J. Colloid Interf. Sci. 433 (1), 16-25 (2014).
27. A. Tamura, H. Tanaka, N. Yui. Supramolecular flower micelle formation of polyrotaxane-containing triblock copolymers prepared from macro-chain transfer agent bearing molecular hooks. Polym. Chem. 5 (15), 4511-420 (2014).
28. A. Tamura, M. Tokunaga, Y. Iwasaki, N. Yui. Spontaneous assembly into pseudopolyrotaxane between cyclodextrins and biodegradable polyphosphoester ionomers. Macromol. Chem. Phys. 215 (7), 648-653 (2014).
29. N. Yokoyama, J.-H. Seo, A. Tamura, Y. Sasaki, N. Yui. Tailoring the supramolecular structure of aminated polyrotaxanes toward enhanced cellular internalization. Macromol. Biosci. 14 (3), 359-368 (2014).
30. A. Tamura, N. Yui. Lysosomal-specific cholesterol reduction by biocleavable polyrotaxanes for ameliorating Niemann-Pick type C disease. Sci. Rep. 4, 4356 (2014).



2013

31. I. Fukumoto, A. Tamura, M. Matsumura, H. Miura, N. Yui. Sensitization potential of dental resins: 2-hydroxyethyl methacrylate and its water-soluble oligomers have immunostimulatory effects. Plos One 8 (11), e82540 (2013).
32. S. Kakinoki, N. Yui, T. Yamaoka. Platelet responses to dynamic biomaterial surfaces with different poly(ethylene glycol) and polyrotaxane molecular architectures constructed on gold substrates. J. Biomater. Appl. 28 (4), 544-551 (2013).
33. A. Tamura, G. Ikeda, J.-H. Seo, K. Tsuchiya, H. Yajima, Y. Sasaki, K. Akiyoshi, N. Yui. Molecular logistics using cytocleavable polyrotaxanes for the reactivation of enzymes delivered in living cells. Sci. Rep. 3, 2252, (2013).
34. S. Kakinoki, J.-H. Seo, Y. Inoue, K. Ishihara, N. Yui, T. Yamaoka. A large mobility of hydrophilic molecules at the outmost layer controls the protein adsorption and adhering behavior with the actin fiber orientation of human umbilical vein endothelial cells. J. Biomater. Sci., Polym. Ed. 24 (11), 1320-1332 (2013)
35. A. Tamura, N. Yui. A supramolecular endosomal escape approach for enhancing gene silencing of siRNA using acid-degradable cationic polyrotaxanes. J. Mater. Chem. B 1 (29), 3535-3544 (2013)
36. J.-H. Seo, S. Kakinoki, Y. Inoue, T. Yamaoka, K. Ishihara, N. Yui. Inducing rapid cellular response on RGD-binding threaded macromolecular surfaces. J. Am. Chem. Soc. 135 (15), 5513-5516 (2013)
37. J.-H. Seo, S. Kakinoki, Y. Inoue, K. Nam, T. Yamaoka, K. Ishihara, A. Kishida, N. Yui. The significance of hydrated surface molecular mobility in the control of the morphology of adhering fibroblasts. Biomaterials 34 (13), 3260-3214 (2013).
38. J.-H. Seo, K. Sakai, N. Yui. Adsorption state of fibronectin on poly(dimethylsiloxane) surfaces with varied stiffness can dominate adhesion density of fibroblasts. Acta Biomater. 9 (3), 5493-5501 (2013).
39. A. Tamura, N. Yui. Cellular internalization and gene silencing of siRNA polyplexes by cytocleavable cationic polyrotaxanes with tailored rigid backbones. Biomaterials 34 (10), 2480-2491 (2013).
40. K. Nagahama, R. Aoki, T. Saito, T. Ouchi, Y. Ohya, N. Yui. Enhanced stereocomplex formation of enantiomeric polylactides grafted on a polyrotaxane platform. Polym. Chem. 4 (6), 1769-1773 (2013)
41. J.-H. Seo, N. Yui. The effect of molecular mobility of supramolecular polymer surfaces on fibroblast adhesion. Biomaterials 34 (1), 55-63 (2013)
42. J.-H. Seo, S. Kakinoki, T. Yamaoka, N. Yui. Movable polyrotaxane surfaces for modulating cellular adhesion via specific RGD-integrin binding. Adv. Sci. Technol. 86, 59-62 (2013).
43. J.-H. Seo, S. Kakinoki, Y. Inoue, T. Yamaoka, K. Ishihara, N. Yui. Designing dynamic surfaces for regulation of biological responses. Soft Matter 8 (20), 5477-5485 (2012).