Chimeric nanobody-decorated liposomes by self-assembly
Menée à l'aide de lignées cellulaires cancéreuses surexprimant HER2 et à l'aide de xénogreffes de tumeurs sur des modèles murins, cette étude met en évidence l'intérêt d'une approche biophysique pour produire des immunoliposomes en une seule étape par auto-assemblage de monocorps chimériques (anticorps à domaine unique) et de liposomes puis met en évidence l'intérêt de ces immunoliposomes pour accroître l'efficacité des médicaments qu'ils transportent
Liposomes as drug vehicles have advantages, such as payload protection, tunable carrying capacity and improved biodistribution. However, due to the dysfunction of targeting moieties and payload loss during preparation, immunoliposomes have yet to be favoured in commercial manufacturing. Here we report a chemical modification-free biophysical approach for producing immunoliposomes in one step through the self-assembly of a chimeric nanobody (cNB) into liposome bilayers. cNB consists of a nanobody against human epidermal growth factor receptor 2 (HER2), a flexible peptide linker and a hydrophobic single transmembrane domain. We determined that 64% of therapeutic compounds can be encapsulated into 100-nm liposomes, and up to 2,500 cNBs can be anchored on liposomal membranes without steric hindrance under facile conditions. Subsequently, we demonstrate that drug-loaded immunoliposomes increase cytotoxicity on HER2-overexpressing cancer cell lines by 10- to 20-fold, inhibit the growth of xenograft tumours by 3.4-fold and improve survival by more than twofold.