Updated on 2022/05/19

写真a

 
LI, Tianshu
 
Affiliation
Faculty of Science and Engineering, Waseda Research Institute for Science and Engineering
Job title
Junior Researcher(Assistant Professor)

Concurrent Post

  • Faculty of Science and Engineering   School of Advanced Science and Engineering

Education

  • 2010
    -
    2013

    Waseda University   Graduate School of Advanced Science and Engineering   Department of Life Science and Medical Bioscience  

  • 2008
    -
    2010

    Graduate School of Peking University   Graduate School of Pharmaceutical Sciences   Department of Medicinal Chemistry  

  • 2004
    -
    2008

    Peking University Health Science Center   School of Pharmaceutical Sciences  

Degree

  • 博士(理学)

Research Experience

  • 2018
    -
    Now

    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
    -
    2018

    早稲田大学ナノ・ライフ創新研究機構   次席研究員

  • 2015
    -
     

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

Professional Memberships

  • 2019
    -
    Now

    日本バイオマテリアル学会

  • 2012
    -
    2015

    American Chemical Society

 

Research Areas

  • Biomaterials

Papers

  • 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  2021.06  [Refereed]

     View Summary

    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  2020.10  [Refereed]

    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  2019.05  [Refereed]

    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.  2019.04  [Refereed]

    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  2018.02

     View Summary

    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 )  2017.09  [Refereed]

     View Summary

    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  2017.07

     View Summary

    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  2017.04  [Refereed]

     View Summary

    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  [Refereed]

     View Summary

    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  2013.04  [Refereed]

  • 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  [Refereed]

     View Summary

    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  2010.11  [Refereed]

    DOI

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Books and Other Publications

Research Projects

  • Development of amino acid-based cationic lipid nanoparticles specialized for cytosolic gene delivery

    Project Year :

    2019.04
    -
    2022.03
     

 

Syllabus

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Teaching Experience

  • Current Topics in Biosciences

    2018
    -
    Now
     

  • Fundamental Bioscience Laboratory

    2018
    -
    Now
     

  • Science and Engineering Laboratory

    2018
    -
    Now
     

  • Molecular Cell Biology

    2018
    -
    Now
     

  • Chemistry and Bioscience Laboratory

    2018
    -
    2019