H2O2-Responsive Nanocarriers Prepared by RAFT-Mediated Polymerization-Induced Self-Assembly of N-(2-(Methylthio)ethyl)acrylamide for Biomedical Applications

Phan, Hien; Cavanagh, Robert; Destouches, Damien; Vacherot, Francis; Brissault, Blandine; Taresco, Vincenzo; Penelle, Jacques; Couturaud, Benoit

Abstract

H2O2-sensitive block copolymer nanoparticles (NPs) composed of a hydrophilic macro-chain transfer agent (macro-CTA) and a hydrophobic thioether-bearing block were prepared by polymerization-induced self-assembly (PISA) approach. The PISA process first involved the chain extension of poly((poly(ethylene glycol) methyl ether methacrylate)-co-(poly(ethylene glycol) methacrylate)) macro-CTA with a H2O2-responsive N-(2-(methylthio)ethyl)acrylamide (MTEAM) monomer, which self-assembled into P((PEGMA-co-PEGMAOH)-b-PMTEAM) block copolymer NPs. The polymerization kinetics indicated the evolution of particle size and morphology from spherical micelles, fused micelles, to vesicles over time. Upon incubation with 0.1 to 10 mM H2O2, spheres were fragmented due to the oxidation of the PMTEAM cores, thus transforming the hydrophobic thioethers into hydrophilic sulfoxides and disassociating the nanocarriers. 43% of the hydrophobic Nile red dye was encapsulated into the spherical micelles and demonstrated a controlled release in H2O2 incubation. Spherical micelles and vesicles displayed no cytotoxicity in MCF-7, DU145, and 22Rv1 cells. Both spheres and vesicles were efficiently internalized into MCF-7 cells, with spheres showing a higher level of uptake than vesicles due to the smaller sizes. In summary, PISA of P((PEGMA-co-PEGMAOH)-b-PMTEAM) allowed the direct formation and loading of hydrophobic dye into spherical micelles, which showed a controlled drug release in H2O2.

Citation

Phan, H., Cavanagh, R., Destouches, D., Vacherot, F., Brissault, B., Taresco, V., Penelle, J., & Couturaud, B. (2022). H2O2-Responsive Nanocarriers Prepared by RAFT-Mediated Polymerization-Induced Self-Assembly of N-(2-(Methylthio)ethyl)acrylamide for Biomedical Applications. ACS Applied Polymer Materials, 4(10), 7778-7789. https://doi.org/10.1021/acsapm.2c01327

• Journal Article Type: Article
• Acceptance Date: Sep 14, 2022
• Online Publication Date: Sep 26, 2022
• Publication Date: Oct 14, 2022
• Deposit Date: Oct 1, 2022
• Publicly Available Date: Sep 27, 2023
• Journal: ACS Applied Polymer Materials
• Print ISSN: 2637-6105
• Electronic ISSN: 2637-6105
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 4
• Issue: 10
• Pages: 7778-7789
• DOI: https://doi.org/10.1021/acsapm.2c01327
• Keywords: Organic Chemistry; Polymers and Plastics; Process Chemistry and Technology
• Public URL: https://nottingham-repository.worktribe.com/output/11756226
• Publisher URL: https://pubs.acs.org/doi/10.1021/acsapm.2c01327