Design of Remote-Controllable Diels-Alder Platform on Magnetic Nanoparticles via Layer-by-Layer Assembly for AC Magnetic Field-Triggered Drug Release.

Diels-Alder chemistry was exploited to develop a remote-controllable drug release platform on magnetic nanoparticles (MNPs). For this purpose, MNPs were decorated with anionic poly(styrenesulfonic acid--furfuryl methacrylate) (poly(SS--FMA)) and cationic poly(allylamine hydrochloride) by layer-by-layer assembly. The decorated MNPs successfully underwent DA reaction to produce covalent bonding between FMA (diene) and maleimide (dienophile)-terminated model drug. Thermal treatment above 80 °C caused the retro Diels-Alder reaction (rDA) between FMA and the drug, resulting in drug release. The retro DA could be also achieved by applying an alternating-current (AC) magnetic field to the decorated MNPs. This could spatially limit the heat generation around MNP without heating entire system. Drug release could be also accelerated with the irradiation time when a threshold temperature was met or exceeded the required energy for rDA reaction. Our results highlight the potential of DA chemistry as a new strategy to provide a remote controllable drug release platform for improving the therapeutic efficiency.