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

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 ¹⁸⁸Re-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 ¹⁸⁸Reliposome were examined using in vivo imaging, bio-distribution, pharmacokinetics, and dosimetry. The results showed that ¹⁸⁸Re-liposome significantly accumulated in the tumor lesion compared to free ¹⁸⁸Re. The circulation time and tumor targeting of ¹⁸⁸Re-liposome were also longer than that of free ¹⁸⁸Re in tumor-bearing mice. The tumor growth was suppressed by ¹⁸⁸Re-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 ¹⁸⁸Re-liposome to regulate downstream genes. Additionally, inhibition of let-7i could reduce the effects of ¹⁸⁸Re-liposome on suppression of tumor growth, suggesting that let-7 family was involved in ¹⁸⁸Re-liposome mediated suppression of tumor growth in vivo. Our data suggest that ¹⁸⁸Re-liposome could be a novel strategy for targeting HNSCC partially via induction of let-7 microRNA.