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

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.).