Shih Y-H, Peng C.L., Luo T-Y, Shieh M.J.
National Taiwan University, TW
Keywords: doxorubicin, micelles, PCNA, rhenium-188
Hepatocellular carcinoma is the third leading cause of cancer deaths in worldwide. In this study, multi-functional micelles loaded with doxorubicin (Dox) and labeled with the radionuclide rhenium-188 (188Re) were developed to provide the combination of chemotherapy and radiotherapy for liver cancer. We prepared Dox loaded DTPA-micelles (Dox-micelles) using DTPA-PEG-PCL by the co-solvent evaporation method. The Dox-micelles were labeled with Re-188. The mice orthotopically implanted with BNL/Luc hepatoma were randomly allocated to four groups for the following respective treatments, including control (n=4), 188Re-perrhenate (n=4), Dox micelles (n=5) and 188Re Dox-micelles (n=5). The biodsitribution and therapeutic efficacy were investigated by γ-counting and long-term therapeutic monitoring in orthotopic model. Bioluminescence imaging of BNL/Luc hepatoma showed the smallest tumor size in 188Re-Dox micelles group (p<0.05). Moreover, 188Re-Dox micelles group had more than thirty days survival, which was significantly different with 188Re-perrhenate and control (p<0.005). Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) shows that 188Re-Dox micelles inhibited the proliferation of BNL/Luc cell comparing with control and 188Re-perrhenate (p<0.001). 188Re Dox-micelles shows a significant inhibitory effect on the tumor growth and extend the survival time in mice hepatoma model. We suggested the multi-functional micelles could apply for the combined therapies of hepatocellular carcinoma.
Journal: TechConnect Briefs
Volume: 1, Nanotechnology 2013: Advanced Materials, CNTs, Particles, Films and Composites (Volume 1)
Published: May 12, 2013
Pages: 385 - 387
Industry sector: Advanced Materials & Manufacturing
Topic: Nanoparticle Synthesis & Applications