A new method to functionalize thermosensitive nanoparticles for biomedical applications

Stimuli-responsive nanoparticles that can undergo changes in their structure in response to a physico-chemical or biological trigger are highly sought materials for advanced drug delivery applications. A new kind of thermally-responsive acrylamide-based nanoparticles exhibiting different thermosensitive behaviour was synthesized via microemulsion polymerization through a core–shell approach for the delivery of peptides and proteins. A new method to functionalize the surface of nanoparticles based on controlled addition of an acrylate active ester (Pentafluorophenyl Methacrylate, PMF) over the course of polymerization was developed. The resulting coated particles were achieved through a core–shell approach, where PFM was used as a linker between the particle's core and the targeting moiety as it easily reacted with the particle's acrylic core and offered a highly reactive ester group towards amines, allowing functionalization with a wide variety of biomolecules. Moreover, nanoparticles' size was tuned by modifying monomer, initiator and cross-linker concentration, whereas LCST can vary depending on monomer ratio (core) and targeting moieties' characteristics (shell). In addition, it was observed that nanoparticles smaller than 200 nm showed an increase in size, which was attributed to a coil-to-globule transition. However, larger nanoparticles showed the opposite behaviour, thus their size decreased at higher temperatures. The approach described here provides versatility for the development of advanced drug delivery systems, allowing appropriate functionalization with a wide range of biomolecules in a fast and simple way.