Reductively and hydrolytically dual degradable nanoparticles by “click” crosslinking of a multifunctional diblock copolymer

Abstract

In this study, we report the synthesis of dual degradable nanoparticles by crosslinking a multifunctional amphiphilic block copolymer through “click” chemistry. Poly(ethylene glycol)-block-poly((ε-caprolactone)-co-(5,5-dibromomethyl trimethylene carbonate)) (mPEG-b-PDBTCL), an amphiphilic block copolymer with multiple bromo groups, was synthesized first by the ring-opening copolymerization of 5,5-dibromomethyl trimethylene carbonate (DBTC) and ε-caprolactone (CL) in the presence of methoxyl poly(ethylene glycol) as macroinitiator and stannous octanoate (Sn(Oct)2) as catalyst. Then the pendant bromo groups were partially transformed to the azide form by reacting with sodium azide under room temperature, to give partially azidated mPEG-b-PDBTCL (mPEG-b-PDBTCL-N3). Then “click” crosslinking was carried out using mPEG-b-PDBTCL-N3 as precursor and propargyl 3,3′-dithiopropionate as crosslinker, resulting in star-shaped nanoparticles bearing multiple bromo groups in the core. This kind of core crosslinked nanoparticle is biodegradable due to the hydrolysis of the poly(ester-carbonate) core. Additionally, depending on the redox-sensitive disulfide crosslinkers, the stable nanoparticles will dissociate into free block copolymers in the presence of 1,4-dithiothreitol (DTT). Furthermore, ammonium groups were introduced into the core covalently by the quaternization reaction between the remaining bromomethyl groups and N,N-dimethylbutylamine. These dual degradable nanoparticles are expected to have potential applications as smart nanovessels for both drug and gene delivery.