Synthesis of a H2O2-responsive thioether-containing alternating copolymer for drug delivery
- 1Guangxi Colleges and Universities Key Laboratory of Natural and Biomedical Polymer Materials, Guangxi Key Laboratory of Optical and Electronic Materials and Devices, College of Materials Science and Engineering, Guilin University of Technology Guilin 541004 China [email protected] [email protected] [email protected].
- 2The First Affiliated Hospital of Harbin Medical University, School of Stomatology, Harbin Medical University Harbin 150001 China.
Abstract
In this work, an amphiphilic alternating copolymer, P(EG-a-BDT), containing thioether functionalities in the main chain was synthesized via thiol-epoxy click polymerization of 1,4-butanedithiol (BDT) and ethylene glycol diglycidyl ether (EGDE) under mild conditions. The chemical structure, molecular weight, and thermal properties of the polymer were characterized by nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA), consistent with the formation of the target copolymer. Owing to its amphiphilic structure, P(EG-a-BDT) self-assembled into spherical micelles with an average diameter of approximately 81.3 nm. Upon exposure to hydrogen peroxide (H₂O₂), the micelles underwent rapid disassembly, which is attributed to the oxidation of hydrophobic thioether groups into hydrophilic sulfoxide moieties. This process was investigated by dynamic light scattering (DLS), transmission electron microscopy (TEM), and ¹H NMR analyses. MTT assays using NIH/3T3 cells indicated good cytocompatibility of the copolymer. Using doxorubicin (DOX) as a model drug, the drug-loading content (DLC) and drug-loading efficiency (DLE) were determined to be 3.67% and 8.52%, respectively. In vitro release studies revealed that DOX was rapidly released under H₂O₂ stimulation, while minimal release was observed in the absence of H₂O₂. Flow cytometry and confocal laser scanning microscopy (CLSM) further confirmed efficient cellular uptake of DOX-loaded P(EG-a-BDT) micelles by HeLa cells as a model cancer cell line. Furthermore, MTT assays demonstrated that DOX-loaded P(EG-a-BDT) micelles exhibited cytotoxicity toward HeLa cells comparable to that of free DOX. These results demonstrate that P(EG-a-BDT) is an oxidation-responsive amphiphilic alternating copolymer capable of H₂O₂-triggered micellar disassembly and controlled drug release, providing a useful platform for the development of oxidation-responsive drug delivery systems.
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BibTeX
@article{luo2026synthesis,
title = {{Synthesis of a H2O2-responsive thioether-containing alternating copolymer for drug delivery}},
author = {Yunjie Luo and Xiang Zhou and Xinyao Wang and Yulin Huang and Ping Huang and Xiaohua Huang and Chanjuan Liu},
journal = {RSC advances},
year = {2026},
month = nov,
doi = {10.1039/d6ra09313b},
url = {https://europepmc.org/article/PMC/PMC13725862},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Synthesis of a H2O2-responsive thioether-containing alternating copolymer for drug delivery
AU - Yunjie Luo
AU - Xiang Zhou
AU - Xinyao Wang
AU - Yulin Huang
AU - Ping Huang
AU - Xiaohua Huang
AU - Chanjuan Liu
PY - 2026
DA - 2026/11/02
JO - RSC advances
DO - 10.1039/d6ra09313b
UR - https://europepmc.org/article/PMC/PMC13725862
AB - In this work, an amphiphilic alternating copolymer, P(EG-a-BDT), containing thioether functionalities in the main chain was synthesized via thiol-epoxy click polymerization of 1,4-butanedithiol (BDT) and ethylene glycol diglycidyl ether (EGDE) under mild conditions. The chemical structure, molecular weight, and thermal properties of the polymer were characterized by nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA), consistent with the formation of the target copolymer. Owing to its amphiphilic structure, P(EG-a-BDT) self-assembled into spherical micelles with an average diameter of approximately 81.3 nm. Upon exposure to hydrogen peroxide (H₂O₂), the micelles underwent rapid disassembly, which is attributed to the oxidation of hydrophobic thioether groups into hydrophilic sulfoxide moieties. This process was investigated by dynamic light scattering (DLS), transmission electron microscopy (TEM), and ¹H NMR analyses. MTT assays using NIH/3T3 cells indicated good cytocompatibility of the copolymer. Using doxorubicin (DOX) as a model drug, the drug-loading content (DLC) and drug-loading efficiency (DLE) were determined to be 3.67% and 8.52%, respectively. In vitro release studies revealed that DOX was rapidly released under H₂O₂ stimulation, while minimal release was observed in the absence of H₂O₂. Flow cytometry and confocal laser scanning microscopy (CLSM) further confirmed efficient cellular uptake of DOX-loaded P(EG-a-BDT) micelles by HeLa cells as a model cancer cell line. Furthermore, MTT assays demonstrated that DOX-loaded P(EG-a-BDT) micelles exhibited cytotoxicity toward HeLa cells comparable to that of free DOX. These results demonstrate that P(EG-a-BDT) is an oxidation-responsive amphiphilic alternating copolymer capable of H₂O₂-triggered micellar disassembly and controlled drug release, providing a useful platform for the development of oxidation-responsive drug delivery systems.
SN - 2046-2069
ER -