JAIST Repository
https://dspace.jaist.ac.jp/Title

温度応答性両性電解質高分子の液-液相分離の機序解明
および応用

Author(s)廣瀬, 智香CitationIssue Date

2024-06

TypeThesis or Dissertation

Text version

ETDURLhttp://hdl.handle.net/10119/19334

RightsDescription

Supervisor: 松村 和明, 先端科学技術研究科, 博士

Japan Advanced Institute of Science and Technology

Abstract
Tomoka Hirose
Polyampholytes, a class of polyelectrolytes characterized by the presence of both anionic and cationicgroups, demonstrate unique pH and temperature responsiveness through interactions the polymers and theirsurrounding solutions or among the polymers' own functional groups. Such responsiveness enables
polyampholytes to undergo phase transitions, making them invaluable in diverse applications ranging fromsmart materials to biomedical engineering. Due to its high biocompatibility, it is being actively researched
as an intelligent material suitable for biomaterials such as drug delivery systems (DDS). Understanding themechanisms driving these stimulus-responsive phase transitions is crucial for the optimization ofpolyampholyte-based materials, as it informs the design and functionalization strategies that tailor theirproperties to specific applications. Furthermore, in recent years, attention has been focused on the behaviorof liquid-liquid phase separation (LLPS) in living organisms such as organelles without membranes. This
interest is driven by the role of LLPS in critical life processes, including metabolism, where it facilitates
the compartmentalization of biochemical reactions without the need for physical barriers.
Polyampholytes are also being studied as model compounds for proteins, offering insights into themolecular dynamics underlying phase separation biology.
In this study, I explore the synthesis and evaluation of ampholyte polymers that exhibit both liquid-liquid
phase separation (LLPS) behavior and temperature responsiveness. We confirmed that by introducing abenzene ring into an ampholyte polymer that causes phase separation behavior due to electrostaticinteractions, stable phase separation behavior can be induced even in salt solvents. Multi-scalemeasurements revealed that the benzene rings play a crucial role during droplet formation and growth stages
likely due to the π-π interaction, thereby stabilizing LLPS behavior. Leveraging the temperature
responsiveness of these polymers, we designed a novel DDS carrier using a composite material withphotothermal properties derived from liquid metal. This approach aimed to ensure a stable, self-sufficient
supply of trigger stimuli, addressing a significant limitation of current DDS technologies. Cell-based
experiments demonstrated the carrier's ability to concentrate drugs effectively, suggesting its potential tominimize side effects associated with drug delivery. These findings not only contribute to our understandingof the fundamental principles governing LLPS in ampholyte polymers but also open new avenues for thedevelopment of safer, more efficient drug delivery technologies. Future research will focus on further
characterizing the interaction mechanisms at play and exploring the clinical applicability of our novel DDS
carrier.
Keywords: Polyampholytes, Liquid-Liquid phase separation, Drug delivery system, Temperature response
polymers, Liquid metals, Biomaterials