Stimuli-responsive poly(N-vinylcaprolactam-co-2-methoxyethyl acrylate) core–shell microgels: facile synthesis, modulation of surface properties and controlled internalisation into cells†

Herein we report the synthesis of biocompatible stimuli-responsive core–shell microgels consisting of a poly(N-vinylcaprolactam) (PVCL) core and a poly(2-methoxyethyl acrylate) (PMEA) corona via one-step surfactant-free precipitation copolymerization. The copolymerization process was investigated by reaction calorimetry, microgel growth was monitored by in situ dynamic light scattering and the chemical structure of core–shell microgels was characterized by Raman spectroscopy. It was possible to incorporate up to 32 mol% MEA into the VCL/MEA microgels without loss of colloidal stability and broadening of the size distribution. The core–shell morphology of microgels was confirmed by transverse magnetization relaxation 1H-NMR, dynamic light scattering (DLS), atomic force microscopy (AFM) and viscosimetry. By means of the NMR data, calorimetry and viscosity measurements it could be shown that MEA is mainly located in the microgel shell. This leads to hindered temperature-induced swelling and collapsing of the PVCL-core, as demonstrated by DLS measurements, due to the fact that the PMEA-shell exhibits a very low LCST around 5 1C. These results could also be confirmed by AFM: an increasing MEA-content leads to the formation of dense and compact core–shell microgels and results in a loss of their softness and deformability. Due to the presence of the PMEA-shell these microgels can be endocytosed much faster by HeLa cells maintaining their viability and can be suitable candidates for the design of drug carriers or imaging/diagnostic systems.