Understanding the Polymer Rearrangement of pH-Responsive Nanoparticles

Abstract

The use of self-assembled nanoparticles for drug delivery has received significant attention in recent years. However, the dynamic nature of self-assembled polymeric systems means there is a need to develop greater understanding of the inherent stability of these systems. In particular, understanding if these materials remain as discrete nanoparticles, or if there is dynamic exchange of material between particles is critical. Herein, we labelled pH-responsive nanoparticles with fluorescent dyes and then investigated the change in fluorescence when the particles were mixed with unlabelled nanoparticles in order to investigate their potential for polymer rearrangement. Nanoparticles were formed by the nanoprecipitation of pH-responsive poly(ethylene glycol)-block-poly(2-(diethylamino)ethyl methacrylate) (PEG-b-PDEAEMA) as the shell and poly(2-(diethylamino)ethyl methacrylate)-random-poly(2-(diisopropylamino)ethyl methacrylate) (PDEAEMA-r-PDPAEMA) as the core. The core and shell were labelled by incorporating pentafluorophenyl methacrylate (PFPMA) in core or shell respectively and then coupling with either Sulfo-cyanine5 amine or Cyanine3 amine. Exchange of material between nanoparticles was probed by tracking changes in the self-quenching of fluorescently labelled polymers in the core of the nanoparticles. The fluorescence intensity of the labelled nanoparticles was stable when mixed with unlabelled nanoparticles at physiological pH (pH 7.4), suggesting there is limited migration of polymers between particles in this system. This study provides important insights into the use of non-crosslinked nanoparticles under biologically relevant conditions.