Theranostics 2018; 8(22):6178-6194. doi:10.7150/thno.29569

Research Paper

Nanosonosensitizers for Highly Efficient Sonodynamic Cancer Theranostics

Ju Huang1, Fengqiu Liu1, Xiaoxia Han1, Liang Zhang1, Zhongqian Hu2, Qinqin Jiang1, Zhigang Wang1, Haitao Ran1, Dong Wang3, Pan Li1✉

1. Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P. R. China;
2. Department of Ultrasound, Zhongda Hospital, Southeast University, Nanjing 210009, P. R. China;
3. Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University Chongqing 400010, P. R. China.

Abstract

Background: Multifunctional nanoplatforms with diagnostic-imaging and targeted therapeutic functionality (theranostics) are of great interest in the field of precision nanomedicine. The emerging sonodynamic therapy (SDT) combined with sonosensitizers under the guidance of photoacoustic (PA) imaging is highly expected to accurately eliminate cancer cells/tissue.

Methods: Unique core/shell-structured theranostic FA-HMME-MNPs-PLGA nanoparticles (FHMP NPs, FA: folate, HMME: hematoporphyrin monomethyl ether, MNPs: melanin nanoparticles, PLGA: poly (lactic-co-glycolic) acid) were constructed by the integration of MNPs (for PA imaging) in the core and HMME in the shell for enhanced PA imaging-guided SDT, which were further functionalized with a tumor-targeting ligand, FA. The PA imaging-guided SDT was systematically and successfully demonstrated both in vitro and in vivo. The high biosafety of FHMP NPs was also systematically evaluated.

Results: The synthesized FHMP NPs with a broad optical absorption not only possess high PA-imaging contrast enhancement capability but also exhibit significant SDT efficiency. Importantly, such a PLGA based nanoplatform improved light stability of HMME, enhancing sonodynamic performance and facilitated delivery of MNPs to the tumor region. Meanwhile, a combined effect between HMME and MNPs was discovered and verified. Furthermore, a sonosensitizer assisted by ultrasound irradiation engenders reactive oxygen species (ROS)-mediated cytotoxicity toward tumor cells/tissue. Both in vitro cell-level and systematic in vivo xenograft evaluations on tumor-bearing mice demonstrated that the selective killing effect of ROS on tumor cells was assisted by FHMP NPs, which played an active role in the suppression of tumor growth with high biosafety.

Conclusion: A theranostic nanoplatform was successfully constructed, achieving PA imaging-guided SDT against breast cancer cells/tissue. More importantly, MNPs and HMME in one platform with combined effect for enhancing PA imaging was demonstrated. This unique theranostic nanoplatform with multiple capabilities paves a new way toward personalized medicine by rational utilization.

Keywords: Nanosonosensitizers, Sonodynamic therapy, Photoacoustic imaging, Melanin, HMME, Nanomedicine

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How to cite this article:
Huang J, Liu F, Han X, Zhang L, Hu Z, Jiang Q, Wang Z, Ran H, Wang D, Li P. Nanosonosensitizers for Highly Efficient Sonodynamic Cancer Theranostics. Theranostics 2018; 8(22):6178-6194. doi:10.7150/thno.29569. Available from http://www.thno.org/v08p6178.htm