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

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 alpha-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 degrees 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 degrees 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.

Automated summary

This study demonstrates the sophisticated combination of smart mesoporous nanocarriers and the MR-FUS technique for precise regulation of drug release kinetics. Utilizing temperature control and phase transition mechanisms, the efficiency of multi-modal drug release is enhanced, showing significant tumor growth inhibition in in vivo experiments.