Poly(ɛ-L-Lysine)-decorated particles with tunable morphology by combination of Ugi multicomponent polymerisation and RAFT-mediated PISA

We report herein the unprecedented combination of Ugi multicomponent reaction (Ugi MCR) and Polymerisation-Induced Self-Assembly (PISA) to fabricate poly(ε-L-Lysine) (PɛLL) decorated amphiphilic nanoparticles. First, by one-pot Ugi MCR of Boc-protected L-lysine with addition of a trithiocarbonate (TTC) compound, a macromolecular chain transfer agent (macroCTA) for Reversible Addition-Fragmentation chain-Transfer (RAFT) polymerisation was synthesised. The obtained PɛLL-TTC is then used for chain extension of the hydrophobic 2-hydroxypropyl methacrylate (HPMA) in water. The reaction proceeds via the PISA mechanism, leading to the formation of amphiphilic block copolymers that self-assemble 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.).