Theranostics 2016; 6(3):404-417. doi:10.7150/thno.13478

Research Paper

A Multifunctional Theranostic Nanoagent for Dual-Mode Image-Guided HIFU/Chemo- Synergistic Cancer Therapy

Nan Zhang1*, Xiaojun Cai2*, Wei Gao1, Ronghui Wang1, Chunyan Xu1, Yuanzhi Yao1, Lan Hao1, Danli Sheng1, Hangrong Chen2✉, Zhigang Wang1✉, Yuanyi Zheng1✉

1. Second Affiliated Hospital of Chongqing Medical University & Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing, 400010, China.
2. State Key Laboratory of High-Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences.
*Nan Zhang and Xiaojun Cai are co-first authors who contributed equally to this study.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See for full terms and conditions.
Zhang N, Cai X, Gao W, Wang R, Xu C, Yao Y, Hao L, Sheng D, Chen H, Wang Z, Zheng Y. A Multifunctional Theranostic Nanoagent for Dual-Mode Image-Guided HIFU/Chemo- Synergistic Cancer Therapy. Theranostics 2016; 6(3):404-417. doi:10.7150/thno.13478. Available from

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High-intensity focused ultrasound (HIFU) is deemed to be a promising noninvasive therapeutic modality for cancers as well as non-neoplastic diseases. However, the accuracy of the technique in the diagnosis and treatment of tumors remains unsatisfactory. HIFU, when combined with multifunctional synergistic agents (SAs), has the potential to be of greater diagnostic and therapeutic efficacy. Here we describe a smart and multifunctional hollow mesoporous Prussian blue (HMPBs) theranostic nanoplatform, the hollow structure of which is capable of encapsulating doxorubicin (DOX) and perfluorohexane (HMPBs-DOX/PFH). In vitro and in vivo studies validated that HMPBs-DOX/PFH can be used as an amplifiable dual-mode imaging contrast agent, which can simultaneously enhance ultrasound (US) and photoacoustic (PA) imaging for guiding and monitoring tumor therapy. When exposed to HIFU, this versatile HMPBs-DOX/PFH agent could increase the cavitation effect and use lower HIFU intensity to achieve coagulative necrosis. Furthermore, it significantly accelerated the release of DOX thereby enhancing chemotherapeutic efficacy and avoiding systemic side effects of the drug. Such a novel theranostic nanoplatform is expected to integrate dual-mode guided imaging with greater therapeutic efficacy and fewer side effects and is very promising for the noninvasive synergistic tumor therapy.

Keywords: Hollow mesoporous Prussian blue, Phase transformation, Photoacoustic imaging, High-intensity focused ultrasound, Theranostics.