Research Article

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2017, 10(3): 834–855

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https://doi.org/10.1007/s12274-016-1339-8

A multifunctional nanoparticle system combines sonodynamic therapy and chemotherapy to treat hepatocellular carcinoma

Yang Liu1,2,§, Guoyun Wan2,§, Hua Guo1, Yuanyuan Liu2, Ping Zhou1,2, Hemei Wang2, Dan Wang2, Sipei Zhang2, Yinsong Wang2 (*), and Ning Zhang1,2 (*)

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1 Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, China
2 Research Center of Basic Medical Science & School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin Medical University, Tianjin 300070, China
§ These authors contributed equally to this work.

Keywords: nanoparticle, sonodynamic therapy, chemotherapy, combination treatment, hepatocellular carcinoma
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ABSTRACT Hepatocellular carcinoma (HCC) is one of the most common and deadly malignancies worldwide. To date, the survival of patients with HCC has not improved because of the insensitivity of HCC to conventional treatments. Sonodynamic therapy (SDT) is a promising new approach that shows remarkable potential in the treatment of HCC. Here, we designed a simple, biocompatible, and multifunctional nanosystem that combines SDT and chemotherapy to treat HCC. This nanosystem, called HPDF nanoparticles, had a core–shell structure in which hematoporphyrin (HP) was complexed with doxorubicin (DOX) to form the hydrophobic core and the surface was coated with Pluronic F68 to form the hydrophilic shell. In HCC cells, HPDF nanoparticles in combination with ultrasonic irradiation (1.0 MHz, 1.5 W/cm2, 30 s) exhibited potent cytotoxicity, resulting from the synergistic effects of a large amount of reactive oxygen species generated from HP and DOX-induced DNA damage. Notably, HPDF nanoparticles in combination with ultrasonic irradiation significantly reversed drug resistance in Nanog-positive cancer stem cells (CSCs) in HCC. In nude mice bearing HCC tumors, HPDF nanoparticles efficiently accumulated in the tumors and reached the maximum levels within 6‒8 h, post intravenous injection. HPDF nanoparticles, in combination with ultrasonic irradiation (1.0 MHz, 3 W/cm2, 5 min), suppressed tumor growth, angiogenesis, and collagen deposition, considerably. In summary, our results show that HPDF nanoparticles can effectively combine SDT and chemotherapy to inhibit HCC growth and progression through multiple mechanisms in both cellular and animal models.
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A multifunctional nanoparticle system combines sonodynamic therapy and chemotherapy to treat hepatocellular carcinoma. Nano Res. 2017, 10(3): 834–855 https://doi.org/10.1007/s12274-016-1339-8

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