LAUSR

N-(2-Hydroxypropyl)methacrylamide (HPMA) is a water soluble monomer used in the synthesis of biocompatible and non-immunogenic polymers. In particular, poly(HPMA) can be exploited to sterically stabilize nanoparticles (NPs) suitable for the delivery of lipophilic therapeutics without the concerns related to the use of the polyethylene glycol (PEG), such as allergic reactions and the accelerated blood clearance effect. In addition, the use of the ring opening polymerization (ROP) of a lactone in the presence of an initiator that bears a double bond and a hydroxyl group is a promising way (the so called “macromonomer method”) to produce oligoester-based monomers and, in turn, to obtain biodegradable NPs via free radical polymerization. However, HPMA cannot be used as initiator being a secondary alcohol and thus hampering the control over the polymer molecular weight (MW). For this reason, in this work, a novel class of amphiphilic block copolymers that consists of a poly(HPMA) backbone and several short oligo(e-caprolactone) side chains were produced via the adoption of the reversible addition–fragmentation chain transfer (RAFT) polymerization and the “inversion” of the macromonomer method. The oligoester was first synthesized via the ROP of e-caprolactone in the presence of a primary alcohol and then attached to HPMA using a succinic acid unit as spacer. The NPs obtained via the self-assembly of these novel block copolymers are designed to degrade into completely water soluble poly(HPMA) chains with a MW lower than the threshold value for the renal excretion. The cytotoxicity of these novel carriers and their ability to load trabectedin, a hydrophobic anticancer therapeutic, were assessed.