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

Authors Shih Y, Peng C, Chiang P, Lin W, Luo T, Shieh M

Received 23 June 2015

Accepted for publication 2 October 2015

Published 16 December 2015 Volume 2015:10(1) Pages 7443—7454

DOI https://doi.org/10.2147/IJN.S91008

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Govarthanan Muthusamy

Peer reviewer comments 3

Editor who approved publication: Dr Lei Yang

Ying-Hsia Shih,1,2 Cheng-Liang Peng,2 Ping-Fang Chiang,1,2 Wuu-Jyh Lin,2 Tsai-Yueh Luo,2,3 Ming-Jium Shieh1,4

1Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan; 2Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan; 3Institute of Radiological Science, Central University, Taichung, Taiwan; 4Department of Oncology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

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

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