Abstract
Choline kinase α1 (ChoKα1) has become an excellent antitumor target. Among all the inhibitors synthetized, the new compound Ff35 shows an excellent capacity to inhibit ChoKα1 activity. However, soluble Ff35 is also capable of inhibiting choline uptake, making the inhibitor not selective for ChoKα1. 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.
Highlights
Chemoresistance to cancer is a major concern [1,2] that has prompted the development of new effective therapies
This study shows that the coupling of the Choline kinase α1 (ChoKα1) inhibitor Ff35 to biomimetic magnetic nanoparticles (BMNPs) offers great advantages
Since the nanocarrier is a magnetic nanoparticle, it opens the possibility of a magnetic guidance to the target site through the application of a continuous magnetic field
Summary
Chemoresistance to cancer is a major concern [1,2] that has prompted the development of new effective therapies. Among those that affect lipid metabolism, whose alteration occurs in many types of cancer [3,4], have gained great attention. The metabolism of choline has been associated with tumor onset and progression In this context, choline kinase α 1 (ChoKα1) isoform has been considered as biomarker of tumor progression and carcinogenesis [5,6,7], and it has emerged as one of the most promising therapeutic target enzymes in cancer.
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