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Circulating Lipoproteins: A Trojan Horse Guiding Squalenoylated Drugs to LDL-Accumulating Cancer Cells.
Sobot, Dunja Mura, Simona Rouquette, Marie Vukosavljevic, Branko Cayre, Fanny Buchy, Eric Pieters, Grégory Garcia-Argote, Sébastien Windbergs, Maike Desmaële, Didier
Sobot, Dunja
Mura, Simona
Rouquette, Marie
Vukosavljevic, Branko
Cayre, Fanny
Buchy, Eric
Pieters, Grégory
Garcia-Argote, Sébastien
Windbergs, Maike
Desmaële, Didier
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2017-07-05
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Abstract
Selective delivery of anticancer drugs to rapidly growing cancercells can be achieved by taking advantage of their high receptor-mediated uptake of low-density lipoproteins (LDLs). Indeed, wehave recently discovered that nanoparticles made of the squa-lene derivative of the anticancer agent gemcitabine (SQGem)strongly interacted with the LDLs in the human blood. In thepresent study, we showed both in vitro and in vivo that suchinteraction led to the preferential accumulation of SQGem incancer cells (MDA-MB-231) with high LDL receptor expression.As a result, an improved pharmacological activity has beenobserved in MDA-MB-231 tumor-bearing mice, an experi-mental model with a low sensitivity to gemcitabine. Accord-ingly, we proved that the use of squalene moieties not onlyinduced the gemcitabine insertion into lipoproteins, but thatit could also be exploited to indirectly target cancer cells in vivo.
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1525-0024