Shell Cross-Linked Nanoparticles Containing Hydrolytically Degradable, Crystalline Core Domains

Abstract

Shell cross-linked knedel-like nanoparticle s (SCKs) possessing an amphiphilic core−shell morphology consisting of a cross-linked shell and a hydrolytically degradable, crystalline core domain were synthesized from poly(ε-caprolactone)- b -poly(acrylic acid) (PCL- b -PAA) amphiphilic diblock copolymers via a two-step process: self-assembly of PCL- b -PAA into polymer micelles followed by cross-linking of the hydrophilic shell layer via condensation reactions between the carboxylic acid functionalities of PAA and the amine groups of 2,2‘-(ethylenedioxy)bis(ethylamine). PCL- b -PAA was prepared from the selective hydrolysis of a poly(ε-caprolactone)- b -poly( tert -butyl acrylate) (PCL- b -P t BA) precursor, which was synthesized by ring opening polymerization (ROP) of ε-caprolactone (ε-CL) followed by atom transfer radical polymerization (ATRP) of tert -butyl acrylate ( t BA). Selective hydrolysis of the tert -butyl ester groups of the P t BA block by reaction with trimethylsilyl iodide (TMSI), followed by reaction with aqueous acid, gave PCL- b -PAA with nearly 100% conversion and minimal cleavage of the PCL chain segments. Alternatively, selective thermal deprotection of the tert -butyl esters was also performed. SCKs prepared from PCL- b -PAA formed globular nanoparticles when deposited from aqueous solution onto a mica surface at room temperature. The effects of copolymer composition and cross-linking extent on the properties of the SCKs were investigated by tapping-mode atomic force microscopy (AFM). The PCL core domains exhibited interesting crystallization and melting behaviors, in which the PCL melting transition temperature increased as the SCK core volume increased. This suggests that the lamellar thicknesses of PCL cores in larger SCKs are greater. The selective hydrolysis of the polyester (PCL) core domain in the presence of amide cross-links throughout the shell layer to yield nanocage structures was studied by 1 H NMR and AFM. The degradation of PCL was monitored by 1 H NMR, from the appearance of the resonance for sodium 6-hydroxyhexanoate under basic hydrolysis conditions. From AFM analysis for the nanoparticles adsorbed onto a mica surface, it was found that, under both acidic and basic hydrolysis conditions, the core-degraded nanocages formed broader structures with decreased height, in comparison with SCKs before core hydrolysis.