{"title":"Orthogonally Functionalizable Redox-Responsive Polymer Brushes: Catch and Release Platform for Proteins and Cells.","authors":"Aysun Degirmenci,Rana Sanyal,Harm-Anton Klok,Amitav Sanyal","doi":"10.1021/jacs.5c05856","DOIUrl":null,"url":null,"abstract":"Polymer brushes engineered to \"specifically capture\" and \"release on demand\" analytes such as dyes, proteins, and cells find biomedical applications ranging from protein immobilization to cell death. Utilizing a disulfide-linker-containing monomer as a building block enables the fabrication of a redox-responsive polymer brush platform with the \"catch and release\" attribute. Herein, thiol-reactive redox-responsive polymer brushes are fabricated using a pyridyl disulfide-based monomer, and their postpolymerization functionalization is demonstrated via thiol-disulfide exchange reaction with thiol-containing dyes, (bio)molecules, and cell adhesive ligands. After establishing reversible conjugation using a fluorescent dye and other model compounds, copolymer brushes postmodified with thiol-containing mannose demonstrated selective immobilization of concanavalin A in the presence of peanut agglutinin. In addition, a thiolated RGD peptide was conjugated to the side chain of polymer brushes to facilitate cell adhesion, followed by on-demand harvesting. To enable localized drug delivery to surface-adhered cells, orthogonal chain end and side chain functionalization using the thiol-Michael addition and thiol-disulfide exchange reaction, respectively, was used to conjugate the cell adhesive RGD peptide and the anticancer drug doxorubicin (DOX). On-demand DOX release and internalization by surface-bound cancer cells were demonstrated via cleavage of disulfide linkages in the presence of a reducing agent. This approach may provide an attractive methodology to deliver therapeutic agents precisely to specific cells.","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":"50 1","pages":""},"PeriodicalIF":15.6000,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the American Chemical Society","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/jacs.5c05856","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Polymer brushes engineered to "specifically capture" and "release on demand" analytes such as dyes, proteins, and cells find biomedical applications ranging from protein immobilization to cell death. Utilizing a disulfide-linker-containing monomer as a building block enables the fabrication of a redox-responsive polymer brush platform with the "catch and release" attribute. Herein, thiol-reactive redox-responsive polymer brushes are fabricated using a pyridyl disulfide-based monomer, and their postpolymerization functionalization is demonstrated via thiol-disulfide exchange reaction with thiol-containing dyes, (bio)molecules, and cell adhesive ligands. After establishing reversible conjugation using a fluorescent dye and other model compounds, copolymer brushes postmodified with thiol-containing mannose demonstrated selective immobilization of concanavalin A in the presence of peanut agglutinin. In addition, a thiolated RGD peptide was conjugated to the side chain of polymer brushes to facilitate cell adhesion, followed by on-demand harvesting. To enable localized drug delivery to surface-adhered cells, orthogonal chain end and side chain functionalization using the thiol-Michael addition and thiol-disulfide exchange reaction, respectively, was used to conjugate the cell adhesive RGD peptide and the anticancer drug doxorubicin (DOX). On-demand DOX release and internalization by surface-bound cancer cells were demonstrated via cleavage of disulfide linkages in the presence of a reducing agent. This approach may provide an attractive methodology to deliver therapeutic agents precisely to specific cells.
期刊介绍:
The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.