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

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.

Nanomaterials as Inhibitors of Epithelial Mesenchymal Transition in Cancer Treatment

“…Different nanomaterials have been exploited to deliver synthetic chemotherapeutics and chemicals inside cancer cells reverting EMT and chemoresistance, and prevent metastasis in a plethora of tumor types [68][69][70][71][72][73][74][75][76][77][78].…”

“…Polyethylene glycol (PEG)-coated 188 Rhenium-liposome has been shown to inhibit EMT in murine models of ovarian tumors [75] and human head and neck squamous cell carcinoma (HNSCC) [76,77], exhibiting killing efficacy and tumor growth delay through induction of let7 miRNA and glycolysis inhibition.…”

Immune activity and biodistribution of polypeptide K237 and folic acid conjugated amphiphilic PEG-PLGA copolymer nanoparticles radiolabeled with 99mTc

“…In this acetone system, the 99m Tc-labeled NPs remain at the point of application (R f = 0.0), while free pertechnetate (R f = 0.8–1.0) and all known chemical forms of 99m Tc-DTPA and 99m Tc-cysteine complexes migrate upward (R f = 0.7–1.0). After developing, each paper was cut into two halves, the top and bottom halves, and radioactivity in each half was measured using a gamma-ray spectrometer [41, 42]. …”

Future trends and emerging issues for nanodelivery systems in oral and oropharyngeal cancer

“…41,60 In in vivo studies, NP-treatment efficiency is assessed by histological examinations of H&E-stained preparations of the sample under light microscopy 61 or through more advanced methods. These include analysis of fluorescent or bioluminescent signals with an in vivo imaging system 62 or Raman spectra differences through Raman spectroscopy. 63 Gold nanorods (GNRs) are preferentially taken up by malignant cells, by using specific ligands for targeted delivery.…”

“…62 siRNA (siVEGFA) was loaded onto lipid-calciumphosphate NPs and combined with photodynamic therapy (PDT), in order to decrease tumor proliferation and promote cellular apoptosis in HNSCC. However, PDT has a hidden facet that promotes hypoxic conditions and leads to overexpression of angiogenic markers like VEGFA.…”