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 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 188Re-liposome 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.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type by incidence globally
The tumors were palpable after five weeks of implantation, and the bioluminescent imaging (BLI) indicated the tumor location in this orthotopic tumor model (Figure 1A). 123I-FIAU is a substrate of herpes simplex virus type 1-thymidine kinase (HSV1-tk) reporter gene that can be used for nanoSPECT/CT imaging of tumor position in vivo
Radiopharmaceutical is a critical alternative of radiotherapy because it depends on the drug accumulation in tumor lesion, and specific radionuclide like 188Re can emit both particles and γ-rays during decay periods for therapy and diagnosis, so called theranosis [28]. 188Re has been conjugated to various materials, including silica coated magnetite and superparamagnetic iron oxide to form nanoparticles for investigating the therapeutic ability in liver cancer cells in vitro [29]
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type by incidence globally. Combined external beam radiation therapy (EBRT) and chemotherapy effectively contribute to the outcome of HNSCC tumor killing [2], the target radionuclide therapy (TRT) has been reported using monoclonal antibodies conjugated radionuclides [3]. It is prerequisite to confirm the antigens of tumors before using TRT, because surface targets would express differently in various types of HNSCC. The radiopharmaceuticals made by conjugating liposome and radionuclide, such as 186Re and 188Re, are considered advantageous for concomitant diagnosis and therapy of diseases in deep tissues through the enhanced permeability and retention (EPR) effect [6, 7]. The pharmaceutical efficacy of liposome conjugated 188Re has been examined in animal models of human colorectal cancer, glioblastomas, esophageal cancer, and lung cancer [8,9,10,11].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
