Dipeptide mimic oligomer transporter mediates intracellular delivery of Cathepsin D inhibitors: A potential target for cancer therapy - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Journal of Controlled Release Année : 2013

Dipeptide mimic oligomer transporter mediates intracellular delivery of Cathepsin D inhibitors: A potential target for cancer therapy

Résumé

Implication of the intracellular proteolytic activity of Cathepsin D (CathD), a lysosomal aspartyl-protease overexpressed in numerous solid tumors, has been evidenced on tumor growth. Its intracellular inhibition by potent inhibitors such as pepstatin constitutes a relevant but challenging molecular target. Indeed the potential of pepstatin as a therapeutic molecule is hampered by its too low intracellular penetration. We addressed this limitation by designing and developing a bioconjugate combining a pepstatin derivative with a new vector of cell penetration (CPNP) specifically targeting the endolysosomal compartment. We showed that this pepstatin conjugate (JMV4463) exhibited high anti-proliferative effect on tumor cell cultures via intracellular CathD inhibition and altered cell cycle associated with apoptotic events in vitro. When tested in mice xenografted with breast cancer cells, JMV4463 delayed tumor emergence and growth.

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Chimie
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Dates et versions

hal-03560280 , version 1 (07-02-2022)

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Marie Maynadier, Lubomir Vezenkov, Muriel Amblard, Vincent Martin, Céline Gandreuil, et al.. Dipeptide mimic oligomer transporter mediates intracellular delivery of Cathepsin D inhibitors: A potential target for cancer therapy. Journal of Controlled Release, 2013, 171 (2), pp.251-257. ⟨10.1016/j.jconrel.2013.07.017⟩. ⟨hal-03560280⟩
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