Study of central nervous system diseases using synthetically functionalized or biologically derived nanoparticles

時間地點：01:40 pm, Jul 23 (Tue), 2024; R1-1042 Conference Room

研討講者：Noriko Nakamura, PhD

July 09, 2024

Developing therapeutic methods for central nervous system (CNS) diseases has been attracted attentions for the purpose of extending healthy life expectancy in this aging society. Blood-brain barrier (BBB), which consists of tight junction of brain capillary endothelial cells (BCECs) and astrocytic end-feet, prevents drugs from penetrating to the brain. Numerous researchers have been developed drug delivery strategies providing improved penetrating efficiency to therapeutic pharmaceutical agents. Among them, strategies utilizing nanoparticles (NPs) have been intensively studied as non-invasive delivery however NP-based CNS therapeutic application has not been launched yet.

In order to obtain comprehensive structural parameters of NPs for efficient drug delivery to the brain, we clarified the effect of charge ratio, ligand density, and mobility of ligand molecules of glucose-modified polyion complex (PIC) polymeric micelles on the efficiency of BBB penetration mediated by glucose transporters [1]. Meanwhile, it has been also suggested that the size of NP is another important parameter for the efficient drug delivery to the brain. For the purpose of investigating size effect on the performance of NPs, we developed facile and wide-range (30-200 nm) size tunable synthetic method of multi-color conjugated polymer NPs (Pdots) as a fluorescent probe [2]. The investigation of size effect on BBB permeability of NPs is expected to be visualized by multi-color size tunable Pdots.

Addition to synthetic NPs, biologically derived NPs have been widely studied not only for delivering drugs to the brain but also for pathological studies of CNS diseases. For example, bacterial extracellular vesicles (BEVs) transferred to the brain have been suggested to play a key role in the brain-gut axis, interaction between CNS and gut microbiota. Herein, the novel strategy to analyze biodistribution of BEVs based on gold NP labeling is proposed. We believe that clarifying the characteristics of BBB permeable BEVs determined by the origin of bacterial cells, the production mechanism, and the state of bacterial cells is expected to reveal mechanism of brain-gut axis and related pathology of CNS diseases.

 

References

[1]     N. Nakamura, Y. Mochida, K. Toh, S. Fukushima, H. Cabral, Y. Anraku, Polymers 2020, 13 (1), 5.

[2]     N. Nakamura, N. Tanaka, S. Ohta, RSC Adv. 2022, 12 (19), 11606-11611.

Noriko Nakamura, PhD

Department of Chemical System Engineering

University of Tokyo

Noriko Nakamura, PhD

PROFESSIONAL EXPERIENCE

PROFESSIONAL EXPERIENCE

Assistant Professor – The University of Tokyo

May 2024 –Present

·            Department of Chemical System Engineering, School of Engineering

April 2023 – Present

·            Institute of Engineering Innovation, School of Engineering

·            Department of Bioengineering, School of Engineering

Postdoctoral Research Fellow – The University of Tokyo

April 2021 – March 2023

·            Institute of Engineering Innovation, School of Engineering

JSPS Research Fellow – The University of Tokyo

April 2018 – March 2021

·            Department of Bioengineering, School of Engineering

EDUCATION

2018 – 2021    Ph. D. in Bioengineering – The University of Tokyo

        Department of Bioengineering, School of Engineering

2016 – 2018    M. S. in Bioengineering – The University of Tokyo

        Department of Bioengineering, School of Engineering

2012 – 2016    B. S. in Chemical System Engineering – The University of Tokyo

        Department of Chemical System Engineering, School of Engineering

SELECTED PUBLICATIONS

·           Nakamura, N.; Ohta, S. Precise Control Methods of the Physicochemical Properties of Nanoparticles for Personalized Medicine. Curr. Opin. Biotechnol. 2024, 87, 103108.

·           Nakamura, N.; Hamada, R.; Kaneko, H.; Ohta, S. Selecting Optimum miRNA Panel for miRNA Signature-Based Companion Diagnostic Model to Predict the Response of R-CHOP Treatment in Diffuse Large B-Cell Lymphoma. J. Biosci. Bioeng. 2023, 135, 341.

·           Nakamura, N.; Ohta, S.; Yamada, M.; Suzuki, Y.; Inagaki, N. F.; Yamaguchi, T.; Ito, T. Development of a Potassium-Ion-Responsive Star Copolymer with Controlled Aggregation/Dispersion Transition. ACS Omega 2023, 8, 1343.

·           Nakamura, N.; Tanaka, N.; Ohta, S. Facile and Wide-Range Size Tuning of Conjugated Polymer Nanoparticles for Biomedical Applications as a Fluorescent Probe. RSC Adv. 2022, 12, 11606.

·           Nakamura, N.; Mochida, Y.; Toh, K.; Fukushima, S.; Cabral, H.; Anraku, Y. Effect of Mixing Ratio of Oppositely Charged Block Copolymers on Polyion Complex Micelles for in Vivo Application. Polymers 2021, 13, 5.