Monomethyl Auristatin E Grafted-Liposomes to Target Prostate Tumor Cell Lines |
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Authors: | Ariana Abawi,Xiaoyi Wang,Julien Bompard,Anna B rot,Valentina Andretto,Leslie Gudimard,Chlo Devillard,Emma Petiot,Benoit Joseph,Giovanna Lollo,Thierry Granjon,Agn s Girard-Egrot,Ofelia Maniti |
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Affiliation: | 1.Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, ICBMS UMR 5246, Univ Lyon, Université Lyon 1, CNRS, F-69622 Lyon, France; (A.A.); (X.W.); (J.B.); (A.B.); (L.G.); (C.D.); (E.P.); (B.J.); (T.G.); (A.G.-E.);2.Laboratoire d’Automatique, de Génie des Procédés et de Génie Pharmaceutique, LAGEPP UMR 5007, Univ Lyon, Université Lyon 1, CNRS, F-69622 Lyon, France; (V.A.); (G.L.) |
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Abstract: | Novel nanomedicines have been engineered to deliver molecules with therapeutic potentials, overcoming drawbacks such as poor solubility, toxicity or short half-life. Lipid-based carriers such as liposomes represent one of the most advanced classes of drug delivery systems. A Monomethyl Auristatin E (MMAE) warhead was grafted on a lipid derivative and integrated in fusogenic liposomes, following the model of antibody drug conjugates. By modulating the liposome composition, we designed a set of particles characterized by different membrane fluidities as a key parameter to obtain selective uptake from fibroblast or prostate tumor cells. Only the fluid liposomes made of palmitoyl-oleoyl-phosphatidylcholine and dioleoyl-phosphatidylethanolamine, integrating the MMAE-lipid derivative, showed an effect on prostate tumor PC-3 and LNCaP cell viability. On the other hand, they exhibited negligible effects on the fibroblast NIH-3T3 cells, which only interacted with rigid liposomes. Therefore, fluid liposomes grafted with MMAE represent an interesting example of drug carriers, as they can be easily engineered to promote liposome fusion with the target membrane and ensure drug selectivity. |
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Keywords: | liposomes drug delivery membrane fluidity Monomethyl Auristatin E |
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