Researcher basic information

• Master of Science, Hokkaido University, Mar. 2002

• https://researchmap.jp/NakSPRGGKh?lang=en

• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=202501018190125245

• 202501018190125245

• nano technology
• Drug Delivery Sstem (DDS)
• Intestinal cell-adapted LNP
• enteric coated preparations
• Lyophilization, Freez drying
• antioxidant
• Plant-adaptive LNP
• mitochondria

• Life Science, Biomaterials
• Life Science, Pharmaceutical chemistry and drug development sciences

• Bachelor's degree program, School of Pharmaceutical Sciences and Pharmacy

Research activity information

• CPP–PEG‐Guided Surface Engineering of Mitochondria Enables Efficient Cellular Uptake and Respiratory Modulation
  Masahiro Shiraishi; Yukari Muramatsu; Akihiro Nakaya; Yuji Maruo; Rick C. Tsai; Masashi Suganuma; Hisashi Ohta; Atsuhito Takeda; Hideyoshi Harashima; Yuma Yamada
  Advanced Materials Interfaces, Wiley, 01 Jul. 2026, [Peer-reviewed]
  English, Scientific journal, ABSTRACT
  
  Mitochondrial transplantation has emerged as a promising strategy for modulating cellular bioenergetics in mitochondrial dysfunction. However, isolated mitochondria suffer from poor stability and limited cellular uptake, restricting their therapeutic application. To address these limitations, we developed a surface engineering strategy that stabilizes isolated mitochondria while enabling interactions with target cells, providing a platform for selective organ‐ and cell‐targeting. Polyethylene glycol (PEG) with lipid/carbon chains was introduced to mitochondria‐associated membrane structures, forming a protective hydration layer on the mitochondrial surface. This PEG layer also serves as a modular platform for functionalization with biomolecules, such as peptides and antibodies, thereby broadening its biomedical applications. In this study, we examined whether mitochondrial function in target cells can be modulated using PEG‐shielded mitochondria functionalized with a cell‐penetrating peptide (CPP) via a maleimide linkage. Our results suggest that CPP‐PEG‐modified mitochondria exhibit efficient cellular internalization and are associated with increased mitochondrial respiratory activity, consistent with intracellular bioenergetic modulation. These findings suggest that spatially controlled presentation of CPP at the terminus of a PEG layer may provide an effective approach for stabilizing isolated mitochondria while modulating intracellular dynamics and functional responses. This surface engineering strategy offers a proof‐of‐concept design framework for mitochondria‐associated engineering and future bioenergetic strategies.
• Nanoparticulation of BCG-CWS for application to bladder cancer therapy
  Takashi Nakamura; Masafumi Fukiage; Megumi Higuchi; Akihiro Nakaya; Ikuya Yano; Jun Miyazaki; Hiroyuki Nishiyama; Hideyuki Akaza; Toshihiro Ito; Hiroyuki Hosokawa; Toshinori Nakayama; Hideyoshi Harashima
  Journal of Controlled Release, 176, 44, 53, Elsevier BV, Feb. 2014, [Peer-reviewed]
  English, Scientific journal
• The liposome incorporating cell wall skeleton of Mycobacterium bovis bacillus Calmette Guéin can directly enhance the susceptibility of cancer cells to lymphokine activated killer cells through up regulation of natural killer group 2 member D ligands
  Jun Miyazaki; Koji Kawai; Takahiro Kojima; Takehiro Oikawa; Akira Joraku; Toru Shimazui; Akihiro Nakaya; Ikuya Yano; Takashi Nakamura; Hideyoshi Harashima; Hideyuki Akaza
  BJU International, 108, 9, 1520, 1526, Wiley, 11 Feb. 2011, [Peer-reviewed]
  English, Scientific journal, OBJECTIVE
  
  • To conduct a preclinical evaluation of the ability of natural killer cells to cytolyze bladder cancer cells that were modified to show enhanced expression of natural‐killer group 2, member D (NKG2D) ligands by R8‐liposome‐bacillus Calmette‐Guéin (BCG)‐cell wall skeleton (CWS) treatment.
  
  MATERIALS AND METHODS
  
  • The T24 cells and RT‐112 cells were co‐cultured with R8‐liposome‐BCG‐CWS and BCG for 2, 4, or 6 h, and then the surface expression of NKG2D ligands was analyzed using TaqMan real‐time quantitative RT‐PCR.
  
  • Peripheral blood mononuclear cells were obtained with a conventional preparation kit, and then lymphokine‐activated killer (LAK) cells were generated from these purified peripheral blood mononuclear cells via interleukin‐2 stimulation.
  
  • The anti‐tumour effect of LAK cells against untreated and R8‐liposome‐BCG‐CWS co‐cultured with cells of the human bladder cancer cell lines T24 and RT‐112 was analyzed using the cytotoxic WST‐8 assay method at 4 h of culture at various effector/target (E : T) ratios.
  
  RESULTS
  
  • Major histocompatibility complex class I‐related chain B (MICB) expression was increased ≈1.5‐fold on T24 cells and RT‐112 cells with BCG.
  
  • UL‐16‐binding protein (ULBP) 1 expression was also increased ≈1.5‐fold on T24 cells and RT‐112 cells with BCG. R8‐liposome‐BCG‐CWS increased the surface expression of MICB 2.2‐fold on T24 cells but did not increase it significantly on RT‐112 cells.
  
  • ULBP1 expression was increased ≈2.2‐fold on RT‐112 cells, although no differences were observed between the expression of ULBP2 and 3 with R8‐liposome‐BCG‐CWS.
  
  • T24 cells that were co‐cultured with R8‐liposome‐BCG‐CWS showed an ≈1.3‐fold increase in sensitivity to cytolysis by LAK cells at an E : T ratio of 4 and RT‐112 cells showed an ≈1.4‐fold increase at an E : T ratio of 2.
  
  CONCLUSIONS
  
  • In the present study, the induction of surface NKG2D ligands by R8‐liposome‐BCG‐CWS rendered cancer cells more susceptible to cytolysis by LAK cells.
  
  • T24 cells and RT‐112 cells, even when cultured singly in the absence of immune cells, can directly respond to R8‐liposome‐BCG‐CWS.
  
  • The results obtained in the present study may therefore indicate a novel adoptive immunotherapy against bladder cancers.
• The Therapeutic Effects of R8-Liposome-BCG-CWS on BBN-Induced Rat Urinary Bladder Carcinoma
  JUN MIYAZAKI; HIROYUKI NISHIYAMA; IKUYA YANO; AKIHIRO NAKAYA; HIDEYASU KOHAMA; KOJI KAWAI; AKIRA JORAKU; TAKASHI NAKAMURA; HIDEYOSHI HARASHIMA; HIDEYUKI AKAZA
  Anticancer Research, 31, 2065, 2072, 2011, [Peer-reviewed]
  Scientific journal
• Alleviating effect of active hexose correlated compound (AHCC) for anticancer drug-induced side effects in non-tumor-bearing mice
  Kota Shigama; Akihiro Nakaya; Koji Wakame; Hiroshi Nishioka; Hajime Fujii
  Journal of Experimental Therapeutics and Oncology, 8, 1, 43, 51, 2009, [Peer-reviewed]
  English, Scientific journal
• Helicobacter pylori CagA induces Ras-independent morphogenetic response through SHP-2 recruitment activation
  Ryouhei Tsutsumi; Kazuyuki Yokoyama; Yumiko Fujii; Susumu Ishikawa; Megumi Higuchi; Atsushi Takahashi; Yo Kurashima; Yasuhiro Teishikata; Shinya Tanaka; Takeshi Azuma; Masanori Hatakeyama
  The Journal of Biological Chemistry, 279, 17, 17205, 17216, 2004, [Peer-reviewed]
  English, Scientific journal

• Development of bladder cancer therapy based on BCG-CWS encapsulating nanoparticle
  中村孝司; 吹上雅文; 中谷彰洋; 矢野郁也; 宮崎淳; 西山博之; 赤座英之; 伊藤俊宏; 細川裕之; 中山俊憲; 原島秀吉, Japanese Journal of Urological Surgery, 27, 3, 338, 339, Feb. 2014
  Japanese
• Therapeutic effect of intravesical instillation of BCG-CWS-loaded octaarginine liposomes in a BBN-induced cancer in rats
  宮崎淳; 河合弘二; 常楽晃; 中村孝司; 原島秀吉; 中谷彰洋; 小濱秀康; 矢野郁也; 赤座英之, Japanese Journal of Urological Surgery, 23, 3, 304, 305, Feb. 2011
  Japanese
• Mouse bladder cancer therapy model using BCG cell wall skeleton encapsulated;liposome vector
  常樂晃; 宮崎淳; 中谷彰洋; 中村孝司; 河合弘二; 矢野郁也; 原島秀吉; 赤座英之, Japanese Journal of Urological Surgery, 23, 2, 184, 186, Feb. 2010
  Japanese
• Variation in tyrosine phosphorylation sites as a determinant of the biological activity of Helicobacter pylori virulence factor CagA
  中谷彰洋; 東秀明; 畠山昌則, Helicobacter Research, 7, 1, 25, 31, 2003, [Lead author]
  Japanese

• Studies on native type BCG-CWS: Immunoreactivity of B-OMS (JBL-107) as a novel adjuvant for immunotherapy
  Kazuhiro Matsuo; Akihiro Nakaya; Yukihiro Shibuya; Yasushi Chuma; Hideyasu Kiyohara; Shuichi Kishimoto; Shoji Fukushima; Makoto Sunagawa
  12th Meeting of the Japanese Vaccine Adjuvant Research Consortium, 22 Jan. 2019, English, Oral presentation
  22 Jan. 2019 - 22 Jan. 2019

  
  Summary
• Studies on native type BCG-CWS: B-OMS (JBL-107) 4. Immunoreactivity of B-OMS as a novel adjuvant for immunotherapy
  Kazuhiro Matsuo; Akihiro Nakaya; Yukihiro Shibuya; Yasushi Chuma; Hideyasu Kiyohara; Shuichi Kishimoto; Shoji Fukushima; Makoto Sunagawa
  12th Meeting of the Japanese Vaccine Adjuvant Research Consortium, 22 Jan. 2019, English, Poster presentation
  22 Jan. 2019 - 22 Jan. 2019

  
  Summary
• Studies on native type BCG-CWS: B-OMS (JBL-107) 3. Physicochemical property / structure of B-OMS
  Yukihiro Shibuya; Yasushi Chuma; Akihiro Nakaya; Kazuhiro Matsuo; Makoto Sunagawa
  12th Meeting of the Japanese Vaccine Adjuvant Research Consortium, 22 Jan. 2019, English, Poster presentation
  22 Jan. 2019 - 22 Jan. 2019

  
  Summary
• Studies on native type BCG-CWS: B-OMS (JBL-107) 2. Formulation of B-OMS
  Yasushi Chuma; Yukihiro Shibuya; Akihiro Nakaya; Kazuhiro Matsuo; Makoto; Sunagawa
  12th Meeting of the Japanese Vaccine Adjuvant Research Consortium, 22 Jan. 2019, English, Poster presentation
  22 Jan. 2019 - 22 Jan. 2019

  
  Summary
• Studies on native type BCG-CWS: B-OMS (JBL-107) 1. Preparation of B-OMS
  Akihiro Nakaya; Yukihiro Shibuya; Yasushi Chuma; Kazuhiro Matsuo; Makoto Sunagawa
  12th Meeting of the Japanese Vaccine Adjuvant Research Consortium, 22 Jan. 2019, English, Poster presentation
  22 Jan. 2019 - 22 Jan. 2019

  
  Summary

• OIL-IN-WATER EMULSION PREPARATION CONTAINING BACTERIAL CELL WALL SKELETON COMPONENT
  Patent right, Akihiro Nakaya; Yukihiro Shibuya; Yasushi Chuma; Makoto Sunagawa; Yoshimoto Sato, Japan BCG Laboratoty
  特願2018-201789, 26 Dec. 2017
  特許6442703
  26 Dec. 2018, Japan BCG Laboratoty