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.