Plasma membrane lipid bilayer is druggable: Selective delivery of gemcitabine-squalene nano-medicine to cancer cells.

Fiche publication

Date publication

décembre 2022

Journal

Biochimica et biophysica acta. Molecular basis of disease

Auteurs

Membres identifiés du Cancéropôle Est :
Pr LIRUSSI Frédéric

Tous les auteurs :
Lirussi F, Pyrshev K, Yesylevskyy S, Rivel T, Lopez T, Coppens E, Mura S, Couvreur P, Ramseyer C

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/36494037

Résumé

Up to now the lipid bilayers were rarely considered as targets in cancer therapy despite pronounced differences in lipid composition between plasma membranes of benign and malignant cells. In this study we demonstrate that the lipid bilayer of the plasma membrane is druggable and suitable for facilitating selective delivery of amphiphilic gemcitabine-squalene nanomedicines to cancer cells. Data from radioactive assays, fluorescent membrane probes and molecular dynamics simulations provide evidence of selective accumulation of gemcitabine-squalene in the plasma membranes with disrupted lipid asymmetry and its subsequent preferential uptake by malignant cells. This causes pronounced cytotoxicity on cancer cells in comparison to their benign counterparts originating from the same tissue.