Therapeutic and scintigraphic applications of polymeric micelles: combination of chemotherapy and radiotherapy in hepatocellular carcinoma

Abstract

This study evaluated a multifunctional micelle simultaneously loaded with doxorubicin (Dox) and labeled with radionuclide rhenium-188 (¹⁸⁸Re) as a combined radiotherapy and chemotherapy treatment for hepatocellular carcinoma. We investigated the single photon emission computed tomography, biodistribution, antitumor efficacy, and pathology of ¹⁸⁸Re-Dox micelles in a murine orthotopic luciferase-transfected BNL tumor cells hepatocellular carcinoma model. The single photon emission computed tomography and computed tomography images showed high radioactivity in the liver and tumor, which was in agreement with the biodistribution measured by γ-counting. In vivo bioluminescence images showed the smallest size tumor (P<0.05) in mice treated with the combined micelles throughout the experimental period. In addition, the combined ¹⁸⁸Re-Dox micelles group had significantly longer survival compared with the control, ¹⁸⁸ReO₄ alone (P<0.005), and Dox micelles alone (P<0.01) groups. Pathohistological analysis revealed that tumors treated with ¹⁸⁸Re-Dox micelles had more necrotic features and decreased cell proliferation. Therefore, ¹⁸⁸Re-Dox micelles may enable combined radiotherapy and chemotherapy to maximize the effectiveness of treatment for hepatocellular carcinoma.

Keywords:

• ¹⁸⁸Re-Dox micelles
• radiotherapeutic
• chemotherapeutic
• hepatocellular carcinoma

Acknowledgments

This research was funded by the National Science Council of the Republic of China (Taiwan) (NSC 102-2320-B-002-038-MY3) and the Ministry of Health and Welfare, Taiwan (MOHW103-TDU-N-211-133006).

Author contributions

Ying-Hsia Shih designed the experiments, wrote the manuscript, and performed the experiments. Cheng-Liang Peng contributed to experimental suggestions and performed the experiments. Ping-Fang Chiang performed the experiments. Wuu-Jyh Lin contributed to experimental suggestions. Tsai-Yueh Luo contributed to experimental design and suggestions, and manuscript revision. Ming-Jium Shieh contributed to experimental suggestions and manuscript revision. All authors contributed toward data analysis, drafting and critically revising the paper, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.