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Nanoparticles carrying fingolimod and methotrexate enables targeted induction of apoptosis and immobilization of invasive thyroid cancer
Abo Akad Univ, Fac Sci & Engn, Cell Biol, Turku, Finland;Univ Turku, Turku Biosci Ctr, Turku, Finland;Abo Akad Univ, Turku, Finland.
Abo Akad Univ, Fac Sci & Engn, Pharmaceut Sci Lab, Turku, Finland.
Abo Akad Univ, Fac Sci & Engn, Cell Biol, Turku, Finland.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi. Univ Turku, Inst Biomed, Turku, Finland.
Vise andre og tillknytning
2020 (engelsk)Inngår i: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 148, s. 1-9Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

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.

sted, utgiver, år, opplag, sider
ELSEVIER , 2020. Vol. 148, s. 1-9
Emneord [en]
Targeted drug delivery, Methotrexate, Fingolimod, Surface functionalization, Folate receptor, Mesoporous silica nanoparticles, Combination chemotherapy, Thyroid cancer, Chicken chorioallantoic membrane
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Identifikatorer
URN: urn:nbn:se:uu:diva-407969DOI: 10.1016/j.ejpb.2019.12.015ISI: 000517851000001PubMedID: 31917332OAI: oai:DiVA.org:uu-407969DiVA, id: diva2:1421355
Forskningsfinansiär
Academy of Finland, 309374Tilgjengelig fra: 2020-04-02 Laget: 2020-04-02 Sist oppdatert: 2020-04-02bibliografisk kontrollert

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