A molecular Trojan Horse to eliminate tumours

Researchers have succeeded in bringing a drug to the centre of its cellular target using a lipid present in blood. This novel procedure has made it possible to enhance the effectiveness of a molecule used in the treatment of numerous cancers.

Most tumour cells need blood lipoproteins to multiply. Starting from this observation, researchers1Institut Galien Paris-Sud (CNRS/Université Paris-Sud/Université Paris-Saclay) have developed a strategy that aims to trick the tumours by combining gemcitabine, an anti-cancer molecule, with squalene, a precursor of cholesterol which, like cholesterol itself, can be transported by lipoproteins. Having noticed that such linkage increases the anti-tumoural activity of gemcitabine by maintaining it for longer in the blood circulatory system, the team sought to determine its mode of action.

To that end, the researchers studied the behaviour of nanoparticles that associate the anti-cancer agent to the cholesterol precursor activity, first in samples of human blood and then in an animal model. The result was that after disaggregation of the nanoparticles in the blood flow, the “squalenized” gemcitabine was immediately captured by lipoproteins. Finally, it is only upon integration into these proteins that the anti-cancer agent can be captured by tumour cells via their lipoprotein receptors. By showing that the active principle of a drug can be inserted into a cell through a molecular intermediary, these studies lay the groundwork for a novel therapeutic concept, which appears to be a true molecular Trojan Horse.

Nature Communications, May 2017