Researcher basic information

• Master's degree, Hokkaido University, Mar. 2011
• Doctoral degree, Hokkaido University, Mar. 2014

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

• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=202501011401840480
• https://www.pharm.hokudai.ac.jp/yakusetu/

• 00986234

• 202501011401840480

• 脂質設計・合成
• イオン化脂質
• ドラッグデリバリーシステム
• 核酸医薬
• Lipid nano particle (LNP)

• Life Science, Clinical pharmacy
• Life Science, Biomaterials
• Life Science, Pharmaceutical analytical chemistry and physicochemistry

Research activity information

• Jun. 2010, 遺伝子・デリバリー勉強会 第10回シンポジウム優秀ポスター賞
• May 2010, 第134回日本薬学会北海道支部例会優秀発表賞

• The effect of guide RNA thermal denaturation on the quality of Cas9 ribonucleoprotein-loaded lipid nanoparticle formulations
  Rina Shimizu; Yuji Kashiwakura; Morisada Hayakawa; Shunsuke Kita; Mina Sato; Masatoshi Maeki; Manabu Tokeshi; Katsumi Maenaka; Tsukasa Ohmori; Yuma Yamada; Hideyoshi Harashima; Yusuke Sato
  RSC PHARMACEUTICS, 3, 1, 27 Jan. 2026
  English, Scientific journal
• Examining the Impact of Storage Conditions on the Stability of a Liquid Formulation of mRNA-Loaded Lipid Nanoparticles
  Mina Sato; Eleni Samaridou; Moritz Beck-Broichsitter; Masatoshi Maeki; Shunsuke Kita; Manabu Tokeshi; Katsumi Maenaka; Hideyoshi Harashima; Yusuke Sato
  Pharmaceutics, 17, 9, 1194, 1194, MDPI AG, 14 Sep. 2025
  Scientific journal, Background/Objectives: This study investigated the effect of storage conditions on mRNA-LNPs in situ via identification of the formulation traits necessary for improving storage stability. Methods: We synthesized an ionizable lipid, namely TOT-28, which has a hydrolysis-susceptible ester bond in its hydrophilic head group that allows it to act as an indicator of the hydrophilic environment within the mRNA-LNPs. LNPs were stored either at 4 or 25 °C for up to 8 weeks to investigate the effect of pH and temperature on ester hydrolysis, internal mRNA integrity, physicochemical properties of the LNPs, and mRNA gene expression. Results: The results indicate that, at 25 °C, a lower buffer pH increases ester hydrolysis, whereas an opposite trend slightly occurs in ester hydrolysis with storage at 4 °C. We also found that TOT-28-based LNPs were less hydrated and microviscosity was higher at 4 °C compared with storage temperature at 25 °C. Therefore, TOT-28-based LNPs seem less sensitive to external buffer solutions because of a higher-order structure when stored at lower temperatures. In addition, we found that LNPs with different ionizable lipid structures exhibit distinct responses to pH changes at specific storage temperatures. Conclusions: Our findings provide novel insights into the appropriate conditions for long-term storage of the mRNA-LNPs as a liquid formulation.
• Splenic B cell-targeting lipid nanoparticles for safe and effective mRNA vaccine delivery.
  Yuichi Suzuki; Mai Yakuwa; Mina Sato; Eleni Samaridou; Moritz Beck-Broichsitter; Masatoshi Maeki; Manabu Tokeshi; Yuma Yamada; Hideyoshi Harashima; Yusuke Sato
  Journal of controlled release : official journal of the Controlled Release Society, 382, 113687, 113687, 03 Apr. 2025, [International Magazine]
  English, Scientific journal, mRNA-loaded lipid nanoparticles (LNPs) have emerged as a potent and versatile platform that underpins the success of mRNA vaccines, but guidelines for designing safe and effective formulations with minimal off-target effects remain unclear. In this study, we focused on a rational design for a novel ionizable lipid library that is based on ionizable tri-oleoyl-tris (iTOT) compounds with a high yield via a simple 2-step synthesis. To further enhance the efficacy and safety of this potent library for vaccine applications, we identified the optimal composition for a vaccine by focusing on the molar ratio of specific lipid excipients in the formulation. This composition brought about a shift in delivery to the spleen, and the LNP formulation, which contained 15 mol% DSPC (15%DSPC-LNPs), was thoroughly taken up by both B cells and other splenic immune cells. This formulation requires neither additional lipid components nor targeting ligand modifications, and it is accompanied by antigen-specific cytotoxic T lymphocyte responses. The rigid, hydrophobic, and charge-neutral surface of 15%DSPC-LNPs minimizes apolipoprotein E-dependent hepatic uptake and maximizes complement receptor-mediated B-cell targeting. Furthermore, as an intramuscularly administered vaccine, 15%DSPC-LNPs induce antigen-specific immune responses and, importantly, results in significantly lower levels of hepatotoxicity compared with that of the mRNA vaccine formulations currently being marketed. In summary, this study demonstrated how the passive targeting of mRNA-LNPs to organs and cells could be regulated by designing novel ionizable lipids combined with adjusting the relative proportions of lipid components. The results of this study also emphasize how selective mRNA delivery to the spleen could avoid the liver, which highlights a promising strategy for the development of safe and effective vaccines.
• Marginal-zone B cells as promising targets of an mRNA-loaded, lipid-nanoparticle cancer vaccine
  Yuichi Suzuki; Mai Yakuwa; Mina Sato; Eleni Samaridou; Moritz Beck-Broichsitter; Masatoshi Maeki; Manabu Tokeshi; Yuma Yamada; Hideyoshi Harashima; Yusuke Sato
  Next Nanotechnology, 8, 100154, 100154, Elsevier BV, 2025
  Scientific journal
• Engineering branched ionizable lipid for hepatic delivery of clustered regularly interspaced short palindromic repeat-Cas9 ribonucleoproteins.
  Haruno Onuma; Rina Shimizu; Yuichi Suzuki; Mina Sato; Hideyoshi Harashima; Yusuke Sato
  iScience, 27, 10, 110928, 110928, 18 Oct. 2024, [International Magazine]
  English, Scientific journal, The delivery of the CRISPR/Cas ribonucleoprotein (RNP) has received attention for clinical applications owing to its high efficiency with few off-target effects. Lipid nanoparticles (LNPs) are potential non-viral vectors for the delivery of RNPs. Herein, we report the engineering of a branched scaffold structure of ionizable lipids for the hepatic delivery of RNPs. Both the total carbon number and branching position were critical for the functional delivery of RNPs. The optimal ionizable lipid exhibited a more than 98% reduction in transthyretin protein after a single dose with no obvious signs of toxicity. The mechanistic study has revealed that optimal LNPs have a unique "flower-like structure" that depends on both the lipid structure and the payload and that these LNPs accumulate in hepatocytes in an apolipoprotein E-independent manner. These results represent a major step toward the realization of in vivo genome editing therapy via RNP delivery using chemically synthesizable LNP formulations.
• An apolipoprotein E modified liposomal nanoparticle: ligand dependent efficiency as a siRNA delivery carrier for mouse-derived brain endothelial cells.
  Mina Tamaru; Hidetaka Akita; Kazuaki Kajimoto; Yusuke Sato; Hiroto Hatakeyama; Hideyoshi Harashima
  International journal of pharmaceutics, 465, 1-2, 77, 82, 25 Apr. 2014, [International Magazine]
  English, Scientific journal, A disorder in the brain endothelium is thought to be closely related to the pathophysiology of brain diseases. A method for delivering nucleic acids (i.e. short interference RNA; siRNA) to the brain endothelium should be an attractive strategy for curing brain disorders. A liposomal nanoparticle containing a proton-ionizable amino lipid was recently developed as a carrier of encapsulated siRNA. The aim of this study was to evaluate the utility of apolipoprotein E (ApoE) as a targeting ligand for mouse brain endothelial cells (MBEC4 cells). The cellular uptake of the ApoE-modified nanoparticles was gradually increased in an ApoE-density dependent manner. Furthermore, the ApoE-modified nanoparticles were taken up via both clathrin and caveolae mediated endocytosis, thus permitting them to avoid lysosomal degradation. Finally, endogenous gene silencing in MBEC4 cells was efficiently achieved depending on the ApoE-modification. Collectively, the ApoE-modified nanoparticle is a promising carrier for delivering nucleic acids to the brain endothelium.
• Application of apolipoprotein E-modified liposomal nanoparticles as a carrier for delivering DNA and nucleic acid in the brain.
  Mina Tamaru; Hidetaka Akita; Taichi Nakatani; Kazuaki Kajimoto; Yusuke Sato; Hiroto Hatakeyama; Hideyoshi Harashima
  International journal of nanomedicine, 9, 4267, 76, 2014, [International Magazine]
  English, Scientific journal, An innovative drug delivery technology is urgently needed to satisfy unmet medical needs in treating various brain disorders. As a fundamental carrier for plasmid DNA or nucleic acids, we developed a liposomal nanoparticle (multifunctional envelope-type nano device [MEND]) containing a proton-ionizable amino lipid (YSK-MEND). Here we report on the impact of apolipoprotein E (ApoE) modification on the function of YSK-MEND in terms of targeting brain cells. The cellular uptake and function of YSK-MEND encapsulating short interference RNA or plasmid DNA were significantly improved as a result of ApoE modification in mouse neuron-derived cell lines (Neuro-2a and CAD). Intracerebroventricular administration of ApoE-modified YSK-MEND (ApoE/YSK-MEND) encapsulating plasmid DNA also resulted in higher transgene expression in comparison with YSK-MEND that was not modified with ApoE. Moreover, observation of fluorescence-labeled ApoE/YSK-MEND and expression of mCherry (fluorescence protein) derived from plasmid DNA indicated that this carrier might be useful for delivering and conferring transgene expression in neural stem cells and/or neural progenitor cells. Thus, this system may be a useful tool for the treatment of neurodegenerative disease.
• Leptin-derived peptide, a targeting ligand for mouse brain-derived endothelial cells via macropinocytosis.
  Mina Tamaru; Hidetaka Akita; Takahiro Fujiwara; Kazuaki Kajimoto; Hideyoshi Harashima
  Biochemical and biophysical research communications, 394, 3, 587, 92, 09 Apr. 2010, [International Magazine]
  English, Scientific journal, Leptin is an appetite regulatory hormone that is secreted into the blood circulation by adipose tissue, and functions in the central nerve system (i.e. hypothalamus) by crossing the blood brain barrier (BBB). In the present study, we investigated the function of a leptin-derived peptide (Lep(70-89)) as a ligand for mouse brain-derived endothelial cells (MBEC4). Lep(70-89)-modified liposomes, prepared with a polyethyleneglycol (PEG) spacer (Lep(70-89)-PEG-LPs) exhibited a significantly higher cellular uptake than peptide-unmodified liposomes (PEG-LPs). Furthermore, cellular uptake was inhibited by amiloride, while no significant inhibitory effect was observed by the presence of chlorpromazine and filipin III, suggesting that macropinocytosis largely contributed to the cellular uptake of Lep(70-89)-PEG-LPs. Imaging studies revealed that Lep(70-89)-PEG-LPs were not colocalized with endosome/lysosomes, whereas neutral dextran (70 kDa) was predominantly colocalized with these compartments. This indicates that Lep(70-89)-PEG-LPs are taken up via macropinocytosis and are subject to non-classical intracellular trafficking, resulting in the circumvention of lysosomal degradation in endothelial cells.

• 優れた保存安定性とmRNA導入効率を両立するLNP製剤の開発
  科学研究費助成事業
  31 Aug. 2023 - 31 Mar. 2025
  佐藤 みな
  当初計画に従い、①新規イオン化脂質の創出と②LNP調製法の検討を実施しつつ、③保存安定性の評価を行った。
  ①新規イオン化脂質の創出：これまでに、保存安定性に優れたイオン化脂質の開発に向け、頭部構造に環状アミン構造を採用した。また、遺伝子発現効率を考慮し、pKaを調節するための置換基を導入した構造を設計した。足場構造はmRNAの保持、導入能を考慮し、mRNAや脂質同士が疎水性相互作用や水素結合可能な構造を設計した。さらに、両者をリンカーでつなぐ方法を確立した。足場構造のみを変えた4種類の脂質を用いてmRNA-LNPを調製し、4℃と25℃で2ヵ月間保存安定性を評価した。その結果、上記脂質を用いたLNPは、COVID-19に対するワクチンにも用いられた脂質からなるLNPよりも、in vivoにおいて長期保存後の遺伝子発現活性が低下しにくいことがわかった。一方、頭部構造に導入した置換基が保存中に加水分解を受けること、足場構造が異なると分解を受ける割合が異なることが判明し、足場構造がLNPを構成する脂質周囲の環境に影響する可能性が示唆された。足場構造に疎水性相互作用や水素結合可能な構造を有する場合、イオン化脂質とmRNAの相互作用が強まる傾向もみられた。
  ②LNP調製法の検討：①で合成した脂質のうちベンチマークとなる足場構造を持つ脂質を用い、保存時緩衝液のpHが安定性に与える影響を4℃と25℃で2ヵ月間評価した。その結果、25℃ではmRNAの完全性や遺伝子発現効率はpHが低いと低下する傾向がみられた。一方、4℃ではみられないことから、LNP構造は保存中の温度により異なる経過をたどり変化する可能性が示唆された。
  ③保存安定性の評価は、mRNA-LNP内部のmRNAの完全性をキャピラリー電気泳動、LNPを構成するイオン化脂質の完全性をLC/ELSDで評価する系を新たに確立した。
  日本学術振興会, 研究活動スタート支援, 北海道大学, 23K19418