Biomimetic Magnetic Nanocarriers Drive Choline Kinase Alpha Inhibitor inside Cancer Cells for Combined Chemo-Hyperthermia Therapy
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AuthorJabalera, Ylenia; Sola Leyva, Alberto; Peigneux, Ana; Vurro, Federica; Iglesias, Guillermo R.; Vílchez García, Jesús; Pérez Prieto, Inmaculada; Aguilar Troyano, Francisco J.; López Cara, Luisa Carlota; Carrasco Jiménez, María Paz; Jiménez López, Concepción
Magnetic nanoparticleChoKa1 inhibitorDrug deliveryBiomimetic
Jabalera, Y., Sola-Leyva, A., Peigneux, A., Vurro, F., Iglesias, G. R., Vilchez-Garcia, J., ... & Jimenez-Lopez, C. (2019). Biomimetic Magnetic Nanocarriers Drive Choline Kinase Alpha Inhibitor inside Cancer Cells for Combined Chemo-Hyperthermia Therapy. Pharmaceutics, 11(8), 408.
SponsorshipThis research was funded by the Ministerio de Economía y Competitividad (CGL2013-46612 and CGL2016-76723 projects), Ramón y Cajal programme (RYC-2014-16901) and the Fondo Europeo de Desarrollo Regional (FEDER). Also, this research was aided by the Andalusian regional government (CTS-236).
Choline kinase a1 (ChoKa1) has become an excellent antitumor target. Among all the inhibitors synthetized, the new compound Ff35 shows an excellent capacity to inhibit ChoKa1 activity. However, soluble Ff35 is also capable of inhibiting choline uptake, making the inhibitor not selective for ChoKa1. In this study, we designed a new protocol with the aim of disentangling whether the Ff35 biological action is due to the inhibition of the enzyme and/or to the choline uptake. Moreover, we offer an alternative to avoid the inhibition of choline uptake caused by Ff35, since the coupling of Ff35 to novel biomimetic magnetic nanoparticles (BMNPs) allows it to enter the cell through endocytosis without interacting with the choline transporter. This opens the possibility of a clinical use of Ff35. Our results indicate that Ff35-BMNPs nanoassemblies increase the selectivity of Ff35 and have an antiproliferative effect. Also, we demonstrate the effectiveness of the tandem Ff35-BMNPs and hyperthermia.