Synthesis of Multifunctional Polymersomes Prepared by Polymerization-Induced Self-Assembly

Phan, Hien; Cavanagh, Robert; Jacob, Philippa; Destouches, Damien; Vacherot, Francis; Brugnoli, Benedetta; Howdle, Steve; Taresco, Vincenzo; Couturaud, Benoit

Abstract

Polymersomes are an exciting modality for drug delivery due to their structural similarity to biological cells and their ability to encapsulate both hydrophilic and hydrophobic drugs. In this regard, the current work aimed to develop multifunctional polymersomes, integrating dye (with hydrophobic Nile red and hydrophilic sulfo-cyanine5-NHS ester as model drugs) encapsulation, stimulus responsiveness, and surface-ligand modifications. Polymersomes constituting poly(N-2-hydroxypropylmethacrylamide)-b-poly(N-(2-(methylthio)ethyl)acrylamide) (PHPMAm-b-PMTEAM) are prepared by aqueous dispersion RAFT-mediated polymerization-induced self-assembly (PISA). The hydrophilic block lengths have an effect on the obtained morphologies, with short chain P(HPMAm)16 affording spheres and long chain P(HPMAm)43 yielding vesicles. This further induces different responses to H2O2, with spheres fragmenting and vesicles aggregating. Folic acid (FA) is successfully conjugated to the P(HPMAm)43, which self-assembles into FA-functionalized P(HPMAm)43-b-P(MTEAM)300 polymersomes. The FA-functionalized P(HPMAm)43-b-P(MTEAM)300 polymersomes entrap both hydrophobic Nile red (NR) and hydrophilic Cy5 dye. The NR-loaded FA-linked polymersomes exhibit a controlled release of the encapsulated NR dye when exposed to 10 mM H2O2. All the polymersomes formed are stable in human plasma and well-tolerated in MCF-7 breast cancer cells. These preliminary results demonstrate that, with simple and scalable chemistry, PISA offers access to different shapes and opens up the possibility of the one-pot synthesis of multicompartmental and responsive polymersomes.

Citation

Phan, H., Cavanagh, R., Jacob, P., Destouches, D., Vacherot, F., Brugnoli, B., Howdle, S., Taresco, V., & Couturaud, B. (2023). Synthesis of Multifunctional Polymersomes Prepared by Polymerization-Induced Self-Assembly. Polymers, 15(14), Article 3070. https://doi.org/10.3390/polym15143070

• Journal Article Type: Article
• Acceptance Date: Jul 12, 2023
• Online Publication Date: Jul 17, 2023
• Publication Date: 2023-07
• Deposit Date: Aug 1, 2023
• Publicly Available Date: Aug 2, 2023
• Journal: Polymers
• Electronic ISSN: 2073-4360
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 14
• Article Number: 3070
• DOI: https://doi.org/10.3390/polym15143070
• Keywords: Polymer-based nanomedicine; polymerization-induced self-assembly (PISA); reactive oxygen species (ROS); hydrogen peroxide (H2O2); responsive nanoparticles; targeted drug delivery
• Public URL: https://nottingham-repository.worktribe.com/output/23220816
• Publisher URL: https://www.mdpi.com/2073-4360/15/14/3070