Stepwise drug release from a nanoplatform under MR-assisted focused ultrasound stimulation.

[Display omitted] • Magnetic resonance technique for temperature-controlled ultrasound irradiation. • Hollow-dendritic-silica-nanoparticles-based smart drug carriers. • Concurrent surfactant removal and α-FeOOH species loading via Fenton reaction. • L-menthol as thermal-sensitive "Flowing Valve" rendering stepwise drug release. • Visualized drug release via magnetic resonance imaging. Focused ultrasound (FUS) controlled drug delivery is maturing towards a highly precise and intelligent approach via the integration of ultrasound-responsive nanocarriers and the state-of-the-art magnetic resonance (MR) technique. Herein, an ultrasound-responsive nanoplatform (Dox@L@FeHD) is developed based on hollow dendritic mesoporous organosilica nanoparticles (HDMONs). Using a facile Fenton reaction, ultrasmall α-FeOOH species are anchored within HDMONs, followed by implanting both doxorubicin (Dox) and L-menthol (LM) to obtain Dox@L@FeHD, which shows a T 1 -T 2 bimodal MR contrast feature. Under mild hyperthermia condition (45 °C), the encapsulated LM undergoes a phase-transition and redistribution ("flowing") within HDMONs, resulting in a rearranged pore structure of Dox@L@FeHD post stimulation. Consequently, Dox shifts from burst release to sustained release, as visualized by MR imaging due to the altered MR contrast feature of Dox@L@FeHD concurrently. In vivo FUS stimulation of Dox@L@FeHD is executed using a self-developed feedback temperature control algorithm to render a constant temperature of 45 °C at the targeted tumor region, thus triggering the in-situ stepwise Dox release, which induces effective retardation of tumor growth. This work demonstrates an elaborate marriage of smart mesoporous nanocarriers and the MR-FUS technique for the accurate regulation of drug release kinetics. [ABSTRACT FROM AUTHOR]