Research Institute for Electronic Science, Hokkaido University


LAST UPDATE 2022/07/13

  • 研究者氏名
    Researcher Name

    テェーマイトリィ・ファーサイ Farsai TAEMAITREE
    助教 Assistant Professor
  • 所属
    Professional Affiliation

    Research Institute for Electronic Science, Hokkaido University

    光科学研究部門 ナノ材料光計測研究分野
    Photonics and Optical Science, Laboratory of Nanomaterials and Nanoscopy
  • 研究キーワード
    Research Keywords

    Drug Delivery Systems
    Surface Functionalization
Research Subject
Intracellular Investigation of Drug Nanoparticles toward Highly Efficient DDSs

研究の背景 Background

Since discovering the enhanced permeability and retention effect, nanoparticle-based drug delivery systems (DDSs) have gained much attention as a chemotherapeutic agent. Due to a significantly increased vascular permeability in tumor tissue and an underdeveloped lymphatic system, nanoparticles (NPs) can passively target and accumulate in tumor tissue without causing drug side effects. Nanocarrier-containing drug molecules (e.g., liposomes, polymer micelles, and dendrimers) have been explored extensively over the past decades. However, these nanocarriers are considered one of the main hindrances to drug delivery applications, possibly causing long-term side effects and increasing systematic toxicity. To overcome this limitation, the concept of alternative carrier-free DDSs composed exclusively of hydrophobic drugs or prodrugs was developed.

研究の目標 Outcome

Despite the impressive therapeutic efficiency of carrier-free DDSs, a lack of knowledge and methodologies concerning the intracellular fate, degradation, and conversion into the active drug of NPs after internalization drastically hinders further developments toward clinical applications. Knowing (i) if NPs enter the cells; (ii) if they are decomposed before entering the plasma membrane or efficiently degraded inside the cells and converted into active drugs; and (iii) if the cellular enzyme level plays a role in these processes, is fundamental for evaluating the suitability of this innovative carrier-free DDSs towards further steps. Herein, we designed carrier-free DDSs for the study based on fluorescence microscopy to unravel the dynamics of NPs inside cancer cells, including internalization, intracellular localization, particle degradation, and therapeutic efficiency.

研究図Research Figure

Fig.1 Design and characterization of FRET prodrug NPs. (A) SN-38-chol prodrug and BPFL-chol molecules were synthesized and reprecipitated to form FRET prodrug NPs; (B) SEM images; (C) related diameter distribution (Gaussian fitting in red)

Fig.2 Intracellular dynamics. FRET prodrug NPs were internalized by human liver cancer cells (1) and their degradation was monitored via FRET (2). The degradation releases SN-38-chol prodrug molecules, that are hydrolyzed by intracellular esterase enzymes (3) into SN-38 active drug molecules, that, in turn, enter the nucleus to perform their therapeutic action (4).

文献 / Publications

Bull. Chem. Soc. Jpn., 92, 1305–1313 (2019)., Nanoscale, 12, 16710–16715 (2020)., Mol. Cryst. Liq. Cryst., 706, 116–121 (2020)., Chem. Lett., 50, 1555-1558 (2021)., J. Cryst. Growth, 572, 126265 (2021).