Nanoparticles carrying fingolimod and methotrexate enables targeted induction of apoptosis and immobilization of invasive thyroid cancer
| Autor: | Cecilia Sahlgren, Erik Niemelä, Nafis A. Rahman, Kati Kemppainen, Diti Desai, Rasmus Niemi, Jessica M. Rosenholm, John E. Eriksson, Milena Doroszko, Kid Törnquist, Ezgi Özliseli |
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| Rok vydání: | 2020 |
| Předmět: |
Pharmaceutical Science
Apoptosis Chick Embryo 02 engineering and technology 030226 pharmacology & pharmacy Chorioallantoic Membrane 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans Neoplasm Invasiveness Thyroid Neoplasms Thyroid cancer Cell Proliferation Fingolimod Hydrochloride business.industry Thyroid disease Folate Receptors GPI-Anchored Thyroid Cancer Combination chemotherapy General Medicine Silicon Dioxide 021001 nanoscience & nanotechnology medicine.disease Xenograft Model Antitumor Assays Methotrexate medicine.anatomical_structure Targeted drug delivery Folate receptor Cancer cell Cancer research Nanoparticles 0210 nano-technology business Biotechnology |
| Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics. 148:1-9 |
| ISSN: | 0939-6411 |
| Popis: | Metastatic tumors are the main cause of cancer-related death, as the invading cancer cells disrupt normal functions of distant organs and are nearly impossible to eradicate by traditional cancer therapeutics. This is of special concern when the cancer has created multiple metastases and extensive surgery would be too dangerous to execute. Therefore, combination chemotherapy is often the selected treatment form. However, drug cocktails often have severe adverse effects on healthy cells, whereby the development of targeted drug delivery could minimize side-effects of drugs and increase the efficacy of the combination therapy. In this study, we utilized the folate antagonist methotrexate (MTX) as targeting ligand conjugated onto mesoporous silica nanoparticles (MSNs) for selective eradication of folate receptor-expressing invasive thyroid cancer cells. The MSNs was subsequently loaded with the drug fingolimod (FTY720), which has previously been shown to efficiently inhibit proliferation and invasion of aggressive thyroid cancer cells. To assess the efficiency of our carrier system, comprehensive in vitro methods were employed; including flow cytometry, confocal microscopy, viability assays, invasion assay, and label-free imaging techniques. The in vitro results show that MTX-conjugated and FTY720-loaded MSNs potently attenuated both the proliferation and invasion of the cancerous thyroid cells while keeping the off-target effects in normal thyroid cells reasonably low. For a more physiologically relevant in vivo approach we utilized the chick chorioallantoic membrane (CAM) assay, showing decreased invasive behavior of the thyroid derived xenografts and an increased necrotic phenotype compared to tumors that received the free drug cocktail. Thus, the developed multidrug-loaded MSNs effectively induced apoptosis and immobilization of invasive thyroid cancer cells, and could potentially be used as a carrier system for targeted drug delivery for the treatment of diverse forms of aggressive cancers that expresses folate receptors. |
| Databáze: | OpenAIRE |
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