Multi-modal responsive magnetic nanoparticle system controlled by intact pseudorotaxane nanovalve

A mechanically interlocking supramolecular nanovalve-coupled mesoporous iron oxide nanoparticles as a multi-stimuli responsive drug release system was constructed. [1]Pseudorotaxane, which is comprised of a cyclohexyl stoppered dialkylammonium axle ( 3 ) and dibenzyl containing [24]crown-8 macrocycle ( 5 ), was successfully tethered to the surface of the mesoporous iron oxide nanoparticles ( meso -Fe 3 O 4 NPs) and acted like an intact nanovalve to enable controlled drug release at the center of the meso -Fe 3 O 4 NPs. In the release mechanism, no nanovalve components were detached during the drug release. This novel nanodevice features both the thread and the crown of a pseudorotaxane covalently linked to the surface of the meso -Fe 3 O 4 NPs. Thanks to the non-polar characteristics of the NPs core and surface, this system may be utilized as a hydrophobic drug carrier. The release profile of the drug loaded meso -Fe 3 O 4 @ 3 ⊂ 5 NPs reveals that the NPs can largely reduce premature drug leakage for up to 88 % at 30 min and 80 % at 90 min. A novel core-satellite Fe 3 O 4 nanocomposite was prepared by self-assembly of drug-loaded meso -Fe 3 O 4 @ 3 ⊂ 5 NPs and ultra-small superparamagnetic iron oxide nanoparticles (USPION@ 7 ); the nanocomposite was successfully applied as a thermo- and ultrasound-responsive drug release system and could function properly in acidic conditions similar with the TME. We anticipate that further optimization of the NPs could potentially generate a smart drug release system applicable to cancer therapy or treatment of other diseases. This work showcases (i) the combination of [1]pseudorotaxane and meso -Fe 3 O 4 NPs generates an elegant nanovalve system, for stimuli-responsive controlled drug release and (ii) how the system can be fine-tuned to become thermo- and ultrasound-responsive in an otherwise hostile environment for biosafe drug delivery. • First intact [1]pseudorotaxane nanovalve tethered on meso -Fe 3 O 4 NPs. • Both axle and crown covalently anchored; no valve components detach. • Premature leakage reduced by up to 88% at 30 min, 80% at 90 min. • Thermo/ultrasound-triggered release: 70% at 43 °C; works at pH 5. • Core–satellite USPION assembly enables AMF heating and 90% release.