当前位置： SCI文献检索 > BIOMACROMOLECULES期刊下所有文献 > Poly( N-isopropylacrylamide)-Based Polymer-Inducing Isothermal Hydrophilic-to-Hydrophobic Phase Transition via Detachment of Hydrophilic Acid-Labile Moiety.

Poly( N-isopropylacrylamide)-Based Polymer-Inducing Isothermal Hydrophilic-to-Hydrophobic Phase Transition via Detachment of Hydrophilic Acid-Labile Moiety.

Abstract：

:The polymerization of N-isopropylacrylamide (NIPAAm) with ionizable monomers results in pH-responsive lower critical solution temperature (LCST) polymer which works in an ionization-dependent manner. However, gradual ionization of the comonomer occurs at a broad pH range due to the electrostatic field generated by the polymers, limiting the extent of LCST shift in response to pH change. Furthermore, excess introduction of comonomer may dull phase transition behavior. Here, we report the development of an ionization-independent LCST polymer that exerts a sharp isothermal hydrophilic-to-hydrophobic phase transition in response to slight pH change. Our polymer has a poly(NIPAAm/2-aminoisoprpylacrylamide (AIPAAm)) (P(NIPAAm/AIPAAm)) backbone that retains the continuous structural similarity of N-alkyl groups for preserving phase transition sensitivity, and primary amine for forming hydrophilic acid-labile 2-propionic-3-methylmaleic (PMM) amide linkage. The PMM moiety improves the polymer's hydrophilicity and drastically increases the LCST. Detachment of the PMM moiety in response to mild acidic condition (pH < 6.8) lowers the LCST to that of original P(NIPAAm/AIPAAm), permitting isothermal pH-responsive phase transition. Utilizing this mechanism, P(NIPAAm/AIPAAm) modified with PMM amide linkage exhibits a sharp hydrophilic-to-hydrophobic transition at a physiological temperature (37 °C) and, strikingly, facilitates interaction with cultured cells. Most importantly, our polymer showed significantly higher accumulation within a solid tumor after systemic injection compared to conventional PNIPAAm, which may be due to its phase transition responding to slightly acidic tumor microenvironment. Thus, this study provides a novel polymer that offers delicate control of LCST and pH-responsiveness suitable for use in even fuzzy biological environments.

journal_name

Biomacromolecules

journal_title

Biomacromolecules

authors

Muttaqien SE,Nomoto T,Takemoto H,Matsui M,Tomoda K,Nishiyama N

doi

10.1021/acs.biomac.8b01465

subject

Has Abstract

pub_date

2019-04-08 00:00:00

pages

1493-1504

issue

eissn

1525-7797

issn

1526-4602

journal_volume

pub_type

杂志文章

在线工具

Poly( N-isopropylacrylamide)-Based Polymer-Inducing Isothermal Hydrophilic-to-Hydrophobic Phase Transition via Detachment of Hydrophilic Acid-Labile Moiety.