Involvement of let-7 microRNA for the therapeutic effects of Rhenium-188-embedded liposomal nanoparticles on orthotopic human head and neck cancer model

// Liang-Ting Lin 1, 2 , Chun-Yuan Chang 1 , Chih-Hsien Chang 3 , Hsin-Ell Wang 1 , Shih-Hwa Chiou 2, 4, 5 , Ren-Shyan Liu 1 , Te-Wei Lee 3 , Yi-Jang Lee 1, 6 1 Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan 2 Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan 3 Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan 4 Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan 5 Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan 6 Biophotonics and Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei, Taiwan Correspondence to: Te-Wei Lee, email: tewei123456@gmail.com Yi-Jang Lee, email: yjlee2@ym.edu.tw Keywords: 188 Re-liposome, HNSCC, orthotopic tumor model, microarray analysis, let-7 microRNA Received: May 20, 2016      Accepted: August 13, 2016      Published: August 29, 2016 ABSTRACT Human head and neck squamous cell carcinoma (HNSCC) is usually treated by surgical resection with adjuvant radio-chemotherapy. In this study, we examined whether the radiopharmaceutical 188 Re-liposome could suppress the growth of HNSCC followed by an investigation of molecular mechanisms. The orthotopic HNSCC tumor model was established by human hypopharyngeal FaDu carcinoma cells harboring multiple reporter genes. The drug targeting and therapeutic efficacy of 188 Re-liposome were examined using in vivo imaging, bio-distribution, pharmacokinetics, and dosimetry. The results showed that 188 Re-liposome significantly accumulated in the tumor lesion compared to free 188 Re. The circulation time and tumor targeting of 188 Re-liposome were also longer than that of free 188 Re in tumor-bearing mice. The tumor growth was suppressed by 188 Re-liposome up to three weeks using a single dose treatment. Subsequently, microarray analysis followed by Ingenuity Pathway Analysis (IPA) showed that tumor suppressor let-7 microRNA could be an upstream regulator induced by 188 Re-liposome to regulate downstream genes. Additionally, inhibition of let-7i could reduce the effects of 188 Re-liposome on suppression of tumor growth, suggesting that let-7 family was involved in 188 Re-liposome mediated suppression of tumor growth in vivo . Our data suggest that 188 Re-liposome could be a novel strategy for targeting HNSCC partially via induction of let-7 microRNA.