Non-invasive stimuli-responsive drug delivery using magnetic fields in conjunction with superparamagnetic nanoparticles offers the potential of spatial and temporal control of drug release. When hyperthermia is not desired and control of the dosage is required, it is necessary to design a platform in which local heating on the nanoscale releases the therapeutic cargo without bulk heating of the surrounding medium. In this work, we report a design using a stimuli-responsive nanoparticle platform to control the dosage of the cargo released by an alternating magnetic field (AMF) actuation. A core@shell structure with a superparamagnetic doped iron oxide (MnFe2O4@CoFe2O4) nanoparticle core in a mesoporous silica shell was synthesized. The core used here has a high saturated magnetization and high specific loss power for heat generation under an AMF. The mesoporous shell has a high cargo carrying capacity. A thermo-responsive molecular-based gatekeeper was modified on the core@shell nanoparticles to regulate the cargo release. The mesoporous structure of the silica shell remained intact after exposing to an AMF, showing that the release of cargo is due to the removal of the gatekeepers instead of the destruction of the structure. Most importantly, we demonstrated the amount of cargo released could be adjusted by the AMF exposure time. By applying multiple sequential exposures of AMF, we were able to release the cargo stepwise and increase the total amount of released cargo. The strategy developed here holds great promise for achieving the dosage, temporal, and spatial control of therapeutics delivery without the risk of overheating the particles’ surroundings.

Spatial, temporal, and dose control of drug delivery using non-invasive magnetic stimulation

2019 Spring National Meeting

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