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Endogenous Catalytic Generation of O2 Bubbles for In Situ Ultrasound-Guided High Intensity Focused Ultrasound Ablation

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† State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, People’s Republic of China
‡ University of Chinese Academy of Sciences, Beijing 100049, People’s Republic of China
§ Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China
*E-mail: [email protected]
*E-mail: [email protected]
Cite this: ACS Nano 2017, 11, 9, 9093–9102
Publication Date (Web):August 10, 2017
https://doi.org/10.1021/acsnano.7b03772
Copyright © 2017 American Chemical Society
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Abstract

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High intensity focused ultrasound (HIFU) surgery generally suffers from poor precision and low efficiency in clinical application, especially for cancer therapy. Herein, a multiscale hybrid catalytic nanoreactor ([email protected], abbreviated as [email protected]) has been developed as a tumor-sensitive contrast and synergistic agent (C&SA) for ultrasound-guided HIFU cancer surgery, by integrating dendritic-structured mesoporous organosilica nanoparticles (MONs) and catalase immobilized in the large open pore channels of MONs. Such a hybrid nanoreactor exhibited sensitive catalytic activity toward H2O2, facilitating the continuous O2 gas generation in a relatively mild manner even if incubated with 10 μM H2O2, which finally led to enhanced ablation in the tissue-mimicking PAA gel model after HIFU exposure mainly resulting from intensified cavitation effect. The [email protected] nanoparticles could be accumulated within the H2O2-enriched tumor region through enhanced permeability and retention effect, enabling durable contrast enhancement of ultrasound imaging, and highly efficient tumor ablation under relatively low power of HIFU exposure in vivo. Very different from the traditional perfluorocarbon-based C&SA, such an on-demand catalytic nanoreactor could realize the accurate positioning of tumor without HIFU prestimulation and efficient HIFU ablation with a much safer power output, which is highly desired in clinical HIFU application.

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The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsnano.7b03772.

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