Zwitterionic thermoresponsive nanocomposites as functional systems for magnetic hyperthermia-activated drug delivery

Abstract

The smart combination of controlled drug delivery and magnetic hyperthermia represents a promising approach for potentiating tumor therapeutic treatments, with minimal adverse effects. Indeed, thermoresponsive nanoparticles enable an on-demand drug release according to their thermal activation, and the polymeric nanosystems characterized by an Upper Critical Solution Temperature (UCST) are leading candidates for hyperthermia-based strategies. Secondly, heating processes promoted by superparamagnetic nanostructures might enable targeted hyperthermic effects, without interfering on healthy cells. In this work, we combined the advantages of the UCST-type nanoparticles and superparamagnetic iron-based nanoclusters to design innovative nanocomposites for tunable drug release, activated by magnetic hyperthermia. The thermoresponsive nanoparticles were obtained via self-assembling of an amphiphilic zwitterionic block copolymer, and the nanoclusters were encapsulated into the polymeric scaffolds via flash nanoprecipitation. The organic and inorganic materials were characterized in terms of composition, size and physicochemical properties, highlighting the potential of the reversible addition–fragmentation chain transfer (RAFT) emulsion polymerization in tuning the copolymer composition and the cloud point of the nanoparticles (investigated range: 30–43 °C). We chose 43 °C as representative temperature of hyperthermia treatment and we validated our nanocomposites as delivery system for paclitaxel, a chemotherapeutic agent, under alternate magnetic field. The combined effect of magnetic hyperthermia and the polymer thermoresponsive behavior ensured an on-demand drug release when the target temperature was achieved, providing an almost complete drug release in the first two hours. Alternatively, without a magnetically-mediated heating, the nanocomposites retained the payload. This could pave the way for the definition of advanced hyperthermia-mediated therapeutic treatments.