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Engineering multiple theranostic modalities into single nanoscale entity holds great potential to rejuvenate cancer treatments; however, enabling the sophisticated spatiotemporal control of each component for maximizing theranostic improvement and minimizing side effects concurrently remains a challenge. Herein, an intelligent detachable "nanorocket" is developed to sequentially manipulate and optimize multi-theranostic processes for magnetic resonance-assisted ultrasound-drug combined therapy (MR-HIFU-Drug). The "nanorocket" is constructed by integrating multi-component (MnCO3, doxorubicin, silica) on the pH-sensitive CaCO3 nanoparticles step by step via cation exchange and controlled heterogeneous nucleation, in which doxorubicin is encapsulated in both carbonates and silica component. The "nanorocket" can initiate sequential detachment in the acidic tumor microenvironment. Specifically, carbonates decompose instantly, releasing Mn2+ as the MR contrast agent and leaving hollow silica nanostructure behind as the HIFU synergistic agent. Consequently, burst release of drug is also triggered, further triggering the degradation of silica, which in turn regulates the slow release of drug from silica matrix. Thus, efficient tumor inhibition is achieved by enhanced HIFU ablation and biphase release of doxorubicin with a step-wise clearance of Mn and Si. This work establishes a system for the systematic spatiotemporal dispatch of diverse theranostic components for the balance of efficacy and safety in cancer theranostics.
This article was published in the following journal.
Name: ACS applied materials & interfaces
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