Template-Free Synthesis of Hollow/Porous Organosilica–Fe₃O₄ Hybrid Nanocapsules toward Magnetic Resonance Imaging-Guided High-Intensity Focused Ultrasound Therapy

Entirely differing from the common templating-based multistep strategy for fabricating multifunctional hollow mesoporous silica nanoparticles (HMSN), a facile and template-free synthetic strategy has been established to construct a unique hollow/mesoporous organosilica nanocapsule (OSNC) concurrently encapsulating both isopentyl acetate (PeA) liquid and superparamagnetic iron oxides inside (denoted as PeA@OSNC). This novel material exhibits ultrasmall and uniform particle size (∼82 nm), high surface area (∼534 m 2 ·g –1 ), and excellent colloidal stability in aqueous solution. The oil-phase PeA with relatively low boiling point (142 °C) and high volatility not only plays a crucial role in formation of a large hollow cavity from the viewpoint of structural design but also enables the PeA@OSNC to act as an efficient enhancement agent in high-intensity focused ultrasound (HIFU) therapy. Moreover, the unique satellite-like distribution of Fe 3 O 4 nanoparticles (NP) on the organosilica shell offered excellent magnetic resonance imaging (MRI) contrast capability of PeA@OSNC in vitro and in vivo. More importantly, such a novel theranostic agent has favorable biosafety, which is very promising for future clinical application in MRI-guided HIFU therapy.