Modular Polymers as a Platform for Cell Surface Engineering: Promoting Neural Differentiation and Enhancing the Immune Response
Yan Gu†,‡, Bing Liu†, Qi Liu†,‡, Yingjie Hang†, Lei Wang†, John L. Brash†,§, Gaojian Chen*,†,‡（陈高健研）, and Hong Chen*,† （陈红）
† The Key Lab of Health Chemistry and Molecular Diagnosis of Suzhou, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren-Ai Road, Suzhou 215123, P. R. China
‡ Center for Soft Condensed Matter Physics and Interdisciplinary Research & School of Physical Science and Technology, Soochow University, Suzhou 215006, P. R. China
§ School of Biomedical Engineering and Department of Chemical Engineering, McMaster University, Hamilton, Ontario L8S4L7, Canada
Y.G. and B.L. contributed equally
ACS Appl. Mater. Interfaces 2019, 11, 47720--47729
Regulating cell behavior and cell fate are of great significance for basic biological research and cell therapy. Carbohydrates, as the key biomacromolecules, play a crucial role in regulating cell behavior. Herein, “modular” glycopolymers were synthesized by reversible addition–fragmentation chain transfer polymerization. These glycopolymers contain sugar units (glucose), anchoring units (cholesterol), “guest” units (adamantane) for host–guest interaction, and fluorescent labeling units (fluorescein). It was demonstrated that these glycopolymers can insert into cell membranes with high efficiency and their residence time on the membranes can be regulated by controlling their cholesterol content. Furthermore, the behavior of the engineered cells can be controlled by modifying with different functional β-cyclodextrins (CD-X) via host–guest interactions with the adamantane units. Host–guest interactions with the modular polymers were demonstrated using CD-RBITC (X = a rhodamine B isothiocyanate). The glycopolymers were modified with CD-S (X = seven sulfonate groups) and CD-M (X = seven mannose groups) and were then attached, respectively, to the surfaces of mouse embryonic stem cells for the promotion of neural differentiation and to the surfaces of cancer cells for the enhancement of the immune response. The combination of multiple anchors and host–guest interactions provides a widely applicable cell membrane modification platform for a variety of applications.