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Interaction of Folic Acid with Nanocrystalline Apatites and Extension to Methotrexate (Antifolate) in View of Anticancer Applications

Sarda, Stéphanie and Iafisco, Michele and Pascaud, Patricia and Adamiano, Alessio and Montesi, Monica and Panseri, Silvia and Marsan, Olivier and Thouron, Carole and Dupret Bories, Agnès and Tampieri, Anna and Drouet, Christophe Interaction of Folic Acid with Nanocrystalline Apatites and Extension to Methotrexate (Antifolate) in View of Anticancer Applications. (2018) Langmuir, 34 (40). 12036-12048. ISSN 0743-7463

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Official URL: https://doi.org/10.1021/acs.langmuir.8b02602


Nanocrystalline apatites mimicking bone mineral represent a versatile platform for biomedical applications thanks to their similarity to bone apatite and the possibility to (multi)functionalize them so as to provide “à la carte” properties. One relevant domain is in particular oncology, where drug-loaded biomaterials and engineered nanosystems may be used for diagnosis, therapy, or both. In a previous contribution, we investigated the adsorption of doxorubicin onto two nanocrystalline apatite substrates, denoted HA and FeHA (superparamagnetic apatite doped with iron ions), and explored these drug-loaded systems against tumor cells. To widen their applicability in the oncology field, here we examine the interaction between the same two substrates and two other molecules: folic acid (FA), often used as cell targeting agent, and the anticancer drug methotrexate (MTX), an antifolate analogue. In a first stage, we investigated the adsorptive behavior of FA (or MTX) on both substrates, evidencing their specificities. At low concentration, typically under 100 mmol/L, adsorption onto HA was best described using the Sips isotherm model, while the formation of a calcium folate secondary salt was evidenced at high concentration by Raman spectroscopy. Adsorption onto FeHA was instead fitted to the Langmuir model. A larger adsorptive affinity was found for the FeHA substrate compared to HA; accordingly, a faster release was noticed from HA. In vitro tests carried out on human osteosarcoma cell line (SAOS-2) allowed us to evaluate the potential of these compounds in oncology. Finally, in vivo (subcutaneous) implantations in the mouse were run to ascertain the biocompatibility of the two substrates. These results should allow a better understanding of the interactions between FA/MTX and bioinspired nanocrystalline apatites in view of applications in the field of cancer.

Item Type:Article
HAL Id:hal-02159915
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:French research institutions > Centre National de la Recherche Scientifique - CNRS (FRANCE)
Other partners > Consiglio Nazionale delle Ricerche - CNR (ITALY)
Université de Toulouse > Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE)
French research institutions > Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE)
Université de Toulouse > Université Toulouse III - Paul Sabatier - UT3 (FRANCE)
Other partners > Centre Hospitalier Universitaire de Toulouse - CHU Toulouse (FRANCE)
Laboratory name:
Deposited On:28 Oct 2019 13:10

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