Magnetic Induction Heating Enables On-Demand Drug Release via Diels–Alder Polymeric Nanocarriers

Abstract

As a stimulus-responsive drug release system, we developed Diels–Alder (DA) induction-activated magnetic nanoparticles (DiMaN). Functionalization of polymer-coated magnetic nanoparticles (mNPs) with drugs via thermoreversible DA coupling enabled release through retro-Diels–Alder (rDA) cleavage upon heating. The (pDMAm-co-pFMA)-b-pAAc polymer supported mNP formation and drug binding. DA coupling with maleimide-functionalized drugs was verified by1H NMR, showing distinct exo (3.23 ppm) and endo (3.48 ppm) signals after 72 h at 37 °C. Approximately 70% release was observed within 15 min at 80 °C, while the complex maintained stability at 40 °C. The superparamagnetic mNPs generated localized heating under an alternating current magnetic field (192 kHz, 480 A), raising the solution temperature by 6 °C within 5 min. The biotin-maleimide complex demonstrated higher release by rDA from furan-containing mNPs (approximately 150 μM) compared to the control group (approximately 103 μM). These results highlight DiMaN as a promising platform for magnetic-controlled, on-demand drug release.