2022/08/17 更新

写真a

リ テンジョ
李 天舒
所属
理工学術院 理工学術院総合研究所
職名
次席研究員(研究院講師)

兼担

  • 理工学術院   先進理工学部

学歴

  • 2010年
    -
    2013年

    早稲田大学   大学院先進理工学研究科   生命医科学専攻  

  • 2008年
    -
    2010年

    北京大学大学院   薬学研究科   薬物化学専攻  

    State Key Laboratory of Natural and Biomimetic Drugs

  • 2004年
    -
    2008年

    北京大学医学部   薬学院  

学位

  • 博士(理学)

経歴

  • 2018年
    -
    継続中

    早稲田大学理工学術院総合研究所   次席研究員(研究院講師)

  • 2014年
    -
    2018年

    早稲田大学ナノ・ライフ創新研究機構   次席研究員

  • 2015年
    -
     

    University of Bonn   The Life & Medical Sciences Institute, Institute of Innate Immunity   客員研究員

所属学協会

  • 2019年
    -
    継続中

    日本バイオマテリアル学会

  • 2012年
    -
    2015年

    American Chemical Society

 

研究分野

  • 生体材料学

論文

  • Arginine-based cationic liposomes accelerate T cell activation and differentiation in vitro

    Tianshu Li, Felix Tolksdorf, Wenhan Sung, Hiroto Sato, Felix J. Eppler, Morihiro Hotta, Waldemar Kolanus, Shinji Takeoka

    International Journal of Pharmaceutics     121917 - 121917  2022年06月  [査読有り]

    担当区分:筆頭著者, 責任著者

    DOI

  • Ultra-Thin Porous PDLLA Films Promote Generation, Maintenance, and Viability of Stem Cell Spheroids

    Ya An Tsai, Tianshu Li, Lucia A. Torres-Fernández, Stefan C. Weise, Waldemar Kolanus, Shinji Takeoka

    Frontiers in Bioengineering and Biotechnology   9  2021年06月  [査読有り]

     概要を見る

    Three-dimensional (3D) culture bridges and minimizes the gap between <italic>in vitro</italic> and <italic>in vivo</italic> states of cells and various 3D culture systems have been developed according to different approaches. However, most of these approaches are either complicated to operate, or costive to scale up. Therefore, a simple method for stem cell spheroid formation and preservation was proposed using poly(D,<sc>L</sc>-lactic acid) porous thin film (porous nanosheet), which were fabricated by a roll-to-roll gravure coating method combining a solvent etching process. The obtained porous nanosheet was less than 200 nm in thickness and had an average pore area of 6.6 μm2 with a porosity of 0.887. It offered a semi-adhesive surface for stem cells to form spheroids and maintained the average spheroid diameter below 100 μm for 5 days. In comparison to the spheroids formed in suspension culture, the porous nanosheets improved cell viability and cell division rate, suggesting the better feasibility to be applied as 3D culture scaffolds.

    DOI

  • Enhanced In Vitro Magnetic Cell Targeting of Doxorubicin-Loaded Magnetic Liposomes for Localized Cancer Therapy

    Eugenio Redolfi Riva, Edoardo Sinibaldi, Agostina Francesca Grillone, Serena Del Turco, Alessio Mondini, Tianshu Li, Shinji Takeoka, Virgilio Mattoli

    Nanomaterials   10 ( 11 ) 2104  2020年10月  [査読有り]

    DOI

  • NLRP3 inflammasome-activating arginine-based liposomes promote antigen presentations in dendritic cells

    Tianshu Li, Matthias Zehner, Jieyan He, Tomasz Próchnicki, Gabor Horvath, Eicke Latz, Sven Burgdorf, Shinji Takeoka

    International Journal of Nanomedicine   14   3503 - 3516  2019年05月  [査読有り]

    担当区分:筆頭著者

    DOI

  • Membrane fusogenic lysine type lipid assemblies possess enhanced NLRP3 inflammasome activation potency

    Jieyan He, Tianshu Li, Tomasz Próchnicki, Gabor Horvath, Eicke Latz, Shinji Takeoka

    Biochemistry and Biophysics Reports   18   100623 - 100623.  2019年04月  [査読有り]

    DOI

  • Lysine-containing cationic liposomes activate the NLRP3 inflammasome: Effect of a spacer between the head group and the hydrophobic moieties of the lipids

    Tianshu Li, Jieyan He, Gabor Horvath, Tomasz Próchnicki, Eicke Latz, Shinji Takeoka

    Nanomedicine: Nanotechnology, Biology, and Medicine   14 ( 2 ) 279 - 288  2018年02月  [査読有り]

    担当区分:筆頭著者, 責任著者

     概要を見る

    Cationic lipids containing lysine head groups and ditetradecyl, dihexadecyl or dioctadecyl glutamate hydrophobic moieties with/without propyl, pentyl or heptyl spacers were applied for the preparation of cationic liposomes using a simple bath type-sonicator. The size distribution, zeta potential, cellular internalization, and cytotoxicity of the liposomes were characterized, and the innate immune stimulation, e.g., the NLRP3 inflammasome activation of human macrophages and THP-1 cells, was evaluated by the detection of IL-1β release. Comparatively, L3C14 and L5C14 liposomes, made from the lipids bearing lysine head groups, ditetradecyl hydrophobic chains and propyl or pentyl spacers, respectively, were the most potent to activate the NLRP3 inflammasome. The possible mechanism includes endocytosis of the cationic liposomes and subsequent lysosome rupture without significant inducement of reactive oxygen species production. In summary, we first disclosed the structural effect of cationic liposomes on the NLRP3 inflammasome activation, which gives an insight into the application of nanoparticles for improved immune response.

    DOI

  • Preparation, Characterization, and Preliminary In Vitro Testing of Nanoceria-Loaded Liposomes

    Agostina Grillone, Tianshu Li, Matteo Battaglini, Alice Scarpellini, Mirko Prato, Shinji Takeoka, Gianni Ciofani

    NANOMATERIALS   7 ( 9 )  2017年09月  [査読有り]

     概要を見る

    Cerium oxide nanoparticles (nanoceria), well known for their pro-and antioxidant features, have been recently proposed for the treatment of several pathologies, including cancer and neurodegenerative diseases. However, interaction between nanoceria and biological molecules such as proteins and lipids, short blood circulation time, and the need of a targeted delivery to desired sites are some aspects that require strong attention for further progresses in the clinical application of these nanoparticles. The aim of this work is the encapsulation of nanoceria into a liposomal formulation in order to improve their therapeutic potentialities. After the preparation through a reverse- phase evaporation method, size, Z-potential, morphology, and loading efficiency of nanoceria-loaded liposomes were investigated. Finally, preliminary in vitro studies were performed to test cell uptake efficiency and preserved antioxidant activity. Nanoceria-loaded liposomes showed a good colloidal stability, an excellent biocompatibility, and strong antioxidant properties due to the unaltered activity of the entrapped nanoceria. With these results, the possibility of exploiting liposomes as carriers for cerium oxide nanoparticles is demonstrated here for the first time, thus opening exciting new opportunities for in vivo applications.

    DOI

  • Effect of the nanoformulation of siRrNAa-lipid assemblies on their cellular uptake and immune stimulation

    Kohei Kubota, Kohei Onishi, Kazuaki Sawaki, Tianshu Li, Kaoru Mitsuoka, Takaaki Sato, Shinji Takeoka

    International Journal of Nanomedicine   12   5121 - 5133  2017年07月  [査読有り]

     概要を見る

    Two lipid-based nanoformulations have been used to date in clinical studies: lipoplexes and lipid nanoparticles (LNPs). In this study, we prepared small interfering RNA (siRNA)-loaded carriers using lipid components of the same composition to form molecular assemblies of differing structures, and evaluated the impact of structure on cellular uptake and immune stimulation. Lipoplexes are electrostatic complexes formed by mixing preformed cationic lipid liposomes with anionic siRNA in an aqueous environment, whereas LNPs are nanoparticles embedding siRNA prepared by mixing an alcoholic lipid solution with an aqueous siRNA solution in one step. Although the physicochemical properties of lipoplexes and LNPs were similar except for small increases in apparent size of lipoplexes and zeta potential of LNPs, siRNA uptake efficiency of LNPs was significantly higher than that of lipoplexes. Furthermore, in the case of LNPs, both siRNA and lipid were effectively incorporated into cells in a co-assembled state
    however, in the case of lipoplexes, the amount of siRNA internalized into cells was small in comparison with lipid. siRNAs in lipoplexes were thought to be more likely to localize on the particle surface and thereby undergo dissociation into the medium. Inflammatory cytokine responses also appeared to differ between lipoplexes and LNPs. For tumor necrosis factor-a, release was mainly caused by siRNA. On the other hand, the release of interleukin-1β was mainly due to the cationic nature of particles. LNPs released lower amounts of tumor necrosis factor-a and interleukin-1β than lipoplexes and were thus considered to be better tolerated with respect to cytokine release. In conclusion, siRNA-loaded nanoformulations effect their cellular uptake and immune stimulation in a manner that depends on the structure of the molecular assembly
    therefore, nanoformulations should be optimized before extending studies into the in vivo environment.

    DOI PubMed

  • Construction and evaluation of pH-sensitive immunoliposomes for enhanced delivery of anticancer drug to ErbB2 over-expressing breast cancer cells

    Tianshu Li, Takuya Amari, Kentaro Semba, Tadashi Yamamoto, Shinji Takeoka

    NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE   13 ( 3 ) 1219 - 1227  2017年04月  [査読有り]

    担当区分:筆頭著者

     概要を見る

    1,5-Dihexadecyl N, N-diglutamyl-lysyl-L-glutamate (GGLG) liposomes were previously developed to enhance drug delivery efficiency in tumor cells owing to its pH-responsive properties. Herein, we report the modification of GGLG liposomes by conjugating a Fab' fragment of an ErbB2 antibody to the terminus of PEG (polyethylene glycol)-lipid (Fab'-GGLGliposomes). The conjugation of Fab' fragments did not affect the antibody activity, drug (doxorubicin, DOX) encapsulation efficiency, stability during storage or pH-sensitivity. However, the binding affinity of Fab'-GGLG liposomes was enhanced to ErbB2-overexpressing HCC1954 cells specifically, and the cell association increased 10-fold in comparison to GGLG liposomes. Consequently, intracellular DOX delivery was enhanced, with an increased cytotoxicity in HCC1954 cells (i.e., IC50 of 1.17 and 3.08 mu g/mL for Fab'-GGLG-DOX and GGLG-DOX liposomes, respectively). Further, a significantly enhanced tumor growth inhibition was obtained in an ErbB2-overexpressing breast cancer-bearing mouse model. Therefore, a potent anticancer drug delivery system was constructed by the immunological modification of pH-sensitive liposomes. (C) 2016 Elsevier Inc. All rights reserved.

    DOI PubMed

  • Enhanced cellular uptake of maleimide-modified liposomes via thiol-mediated transport

    Tianshu Li, Shinji Takeoka

    INTERNATIONAL JOURNAL OF NANOMEDICINE   9   2849 - 2861  2014年  [査読有り]

    担当区分:筆頭著者

     概要を見る

    With a small amount of maleimide modification on the liposome surface, enhanced cellular uptake of liposomes and drug-delivery efficiency can be obtained both in vitro and in vivo. Herein, we describe the mechanisms underlying this enhanced cellular uptake. Suppression of the cellular uptake of maleimide-modified liposomes (M-GGLG, composed of 1,5-dihexadecyl N, N-diglutamyl-lysyl-L-glutamate [GGLG]/cholesterol/poly(ethylene glycol) 1,2- distearoyl-sn-glycero-3-phosphoethanolamine [PEG(5000)-DSPE]/maleimide [M]-PEG(5000) -Glu2C(18) at a molar ratio of 5: 5: 0.03: 0.03) caused by temperature block and addition of serum was alleviated compared with that of liposomes without maleimide modification (GGLG liposomes, -composed of GGLG/cholesterol/PEG(5000)-DSPE/PEG(5000)-Glu2C(18) at a molar ratio of 5: 5: 0.03: 0.03). When 0.01 nM N-ethylmaleimide was used to pre-block cellular thiols, the cellular uptake of M-GGLG liposomes was decreased to approximately 70% in HeLa, HCC1954, MDA-MB-468, and COS-7 cell lines. Moreover, inhibition of a thiol-related reductase such as protein disulfide isomerase resulted in a 15%-45% inhibition of the cellular uptake of M-GGLG liposomes, whereas GGLG liposomes were not influenced. Further, single and mixed inhibitors of clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis did not efficiently inhibit the cellular uptake of M-GGLG liposomes. Using confocal microscopy, we verified that M-GGLG liposomes were localized partially in lysosomes after inhibition of the mentioned conventional endocytic pathways. Therefore, it was hypothesized that the mechanisms underlying the enhanced cellular uptake of liposomes by maleimide modification was thiol-mediated membrane trafficking, including endocytosis and energy-independent transport.

    DOI

  • In vitro and in vivo evaluation of maleimide-modified liposome for drug delivery

    Tianshu Li, Shinji Takeoka

    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY   245  2013年04月

    担当区分:筆頭著者

  • A novel application of maleimide for advanced drug delivery: in vitro and in vivo evaluation of maleimide-modified pH-sensitive liposomes

    Tianshu Li, Shinji Takeoka

    INTERNATIONAL JOURNAL OF NANOMEDICINE   8   3855 - 3866  2013年  [査読有り]

    担当区分:筆頭著者

     概要を見る

    Maleimide is a stable and easy-to-handle moiety that rapidly and covalently conjugates thiol groups of cysteine residues in proteins or peptides. Herein, we use maleimide to modify the surface of liposomes in order to obtain an advanced drug delivery system. Employing a small amount (0.3 mol%) of maleimide-polyethylene glycol (PEG) to modify the surface of the liposomes M-GGLG-liposomes, composed of 1,5-dihexadecyl N,N-diglutamyl-lysyl-L-glutamate (GGLG)/cholesterol/poly(ethylene glycol) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (PEG(5000)-DSPE)/maleimide-PEG(5000)-Glu2C(18) at a molar ratio of 5:5:0.03:0.03, drug delivery efficiency was remarkably improved both in vitro and in vivo compared to unmodified liposomes (GGLG-liposomes, composed of GGLG/cholesterol/PEG(5000)-DSPE/PEG(5000)-Glu2C(18) at a molar ratio of 5: 5: 0.03: 0.03). Moreover, this modification did not elicit any detectable increase in cytotoxicity. The maleimide-modification did not alter the physical characteristics of the liposomes such as size, zeta potential, pH sensitivity, dispersibility and drug encapsulation efficiency. However, M-GGLG-liposomes were more rapidly (&gt;= 2-fold) internalized into HeLa, HCC1954, and MDA-MB-468 cells compared to GGLG-liposomes. In vivo, M-GGLG-liposomes encapsulating doxorubicin (M-GGLG-DOX-liposomes) also showed a more potent antitumor effect than GGLG-DOX-liposomes and the widely used 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)-DOX-liposomes after two subcutaneous injections around breast cancer tissue in mice. The biodistribution of liposomes in this model was observed using an in vivo imaging system, which showed that M-GGLG-liposomes were present for significantly longer at the injection site compared to GGLG-liposomes. The outstanding biological functions of the maleimide-modified liposomes as a novel drug delivery system make them ideally suited to a wide range of applications.

    DOI

  • A new strategy for the synthesis of 3-deazaneplanocin A

    Li, Tianshu, Xing, Lei, Lin, Guichun, Guan, Zhu, Yang, Zhenjun

    Journal of Chinese Pharmaceutical Sciences   19 ( 6 ) 436 - 442  2010年11月  [査読有り]

    担当区分:筆頭著者

    DOI

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書籍等出版物

共同研究・競争的資金等の研究課題

  • サイトゾルデリバリーに特化したゲノム編集用ナノ粒子の構築

    研究期間:

    2019年04月
    -
    2022年03月
     

     概要を見る

    核酸医薬品やゲノム編集による遺伝子治療か注目されているが、細胞内で十分に機能させるためには優れたサイトゾル運搬効率を持つ運搬体の開発が必要である。本研究では、膜融合性が高いカチオン性アミノ酸型脂質と核酸を混合してサイトゾルドラッグデリバリーシステムを新たに開発する。そして、ケノム編集に向けた核酸/脂質複合ナノ粒子について、分子や分子集合体の構造が細胞内でのケノム編集活性に及ぼす影響について明らかにする。Cationic liposomes are capable to carry nucleic acids to enhance their cellular uptake. Lipid structure determines the interaction of liposomes with cells, which subsequently affects the performance of cargoes. In 2019 fiscal year, several types of arginine- and lysine-based cationic liposomes were prepared and studied for their cellular uptake route and efficiency, membrane fusogenic potency or cytosolic release, as well as their immunoactivities in THP-1 cells, Jurkat cells or HeLa cells. It has been confirmed that regardless of the head group, the spacer and hydrophobic chains of the lipids greatly affected the cellular interaction of the liposomes. The key factor of lipid that is crucial for regulating the cell entry route of liposomes is still under investigation.As planned, through the study of membrane fusogenic potency of a series of cationic liposomes in various types of cells, the lipids that largely promote liposome fusion with plasma membrane have been identified.The selected lipids will be synthesized and used to fabricate with nucleic acids into lipid nanoparticles (LNPs). Other components such as cholesterol and PEG-lipids may also be involved for efficient cargo loading. The preparation conditions such as the lipid composition and concentration, cationic lipid/nucleic acid (N/P) ratio, and buffer components will be studied to regulate the physical properties of LNPs, including size, zeta potential, stability and recovery rate of nucleic acids. Moreover, the intracellular trafficking will be investigated by labeling the lipids and/or nucleic acids with fluorescent probes to evaluate the cellular uptake efficiency, membrane fusogenic potency or cytosolic release

 

現在担当している科目

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担当経験のある科目(授業)

  • Current Topics in Biosciences

    2018年
    -
    継続中
     

  • Fundamental Bioscience Laboratory

    2018年
    -
    継続中
     

  • Science and Engineering Laboratory

    2018年
    -
    継続中
     

  • Molecular Cell Biology

    2018年
    -
    継続中
     

  • Laboratory for Advanced Science and Engineering

    2022年
    -
     
     

  • Chemistry and Bioscience Laboratory

    2018年
    -
    2019年
     

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