Poly(ε-l-lysine)-decorated particles with a tunable morphology by a combination of Ugi multicomponent polymerisation and RAFT-mediated PISA

Nguyen, Thi Phuong Thu; Lei, Lei; Dixon, Emily G.; Le Coeur, Clémence; Taresco, Vincenzo; Debuigne, Antoine; Couturaud, Benoit

Abstract

We report herein the unprecedented combination of the Ugi multicomponent reaction (Ugi MCR) and Polymerisation-Induced Self-Assembly (PISA) to fabricate poly(ε-L-lysine) (PεLL) decorated amphiphilic nanoparticles. First, using the one-pot Ugi MCR of Boc-protected L-lysine with the addition of a trithiocarbonate (TTC) compound, a macromolecular chain transfer agent (macroCTA) for Reversible Addition–Fragmentation chain-Transfer (RAFT) polymerisation was synthesised. The obtained PεLL-TTC was then used for chain extension of the hydrophobic 2-hydroxypropyl methacrylate (HPMA) in water. The reaction proceeded via the PISA mechanism, leading to the formation of amphiphilic block copolymers that self-assembled into a variety of morphologies—including spheres, short worm-like structures, and vesicles—spanning sizes from below 100 nm to over 1 μm. This work showcases a proof-of-concept to prepare water-dispersed nanoparticles decorated with polypeptoids, which are highly desired in biological applications (e.g. stealth-cargo in nanomedicine, bio-separation, antibacterial coating, etc.).

Citation

Nguyen, T. P. T., Lei, L., Dixon, E. G., Le Coeur, C., Taresco, V., Debuigne, A., & Couturaud, B. (2025). Poly(ε-l-lysine)-decorated particles with a tunable morphology by a combination of Ugi multicomponent polymerisation and RAFT-mediated PISA. Polymer Chemistry, https://doi.org/10.1039/D5PY00384A

• Journal Article Type: Article
• Acceptance Date: May 26, 2025
• Online Publication Date: May 30, 2025
• Publication Date: May 30, 2025
• Deposit Date: Jun 16, 2025
• Publicly Available Date: May 31, 2026
• Journal: Polymer Chemistry
• Print ISSN: 1759-9954
• Electronic ISSN: 1759-9962
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1039/D5PY00384A
• Public URL: https://nottingham-repository.worktribe.com/output/50437980
• Publisher URL: https://pubs.rsc.org/en/content/articlelanding/2025/py/d5py00384a