Vectorisation de complexes ferrocéniques par les nanocapsules lipidiques pour le traitement du cancer

Le résumé fourni par la source

The aim of this work is the preclinical evaluation of three ferrocenyl complexes (FcOHTam, FcdiOH and ansa-FcdiOH) formulated into lipid nanocapsules (LNCs) for oncology purposes. Firstly, the anticancer activity of the ferrocifens is demonstrated on a triple negative breast cancer model with a significant delay of the tumor growth upon administration of LNCs loaded with FcOHTAM. In order to enhance the passive tumoral targeting, the second part is dedicated to the development of stealth LNCs through a one-step (OS) formulation process. These OS LNCs showed an extended blood circulation time and maintained their integrity several hours after intravenous (iv) injection, as observed by FRET imaging. Additionally, repeated injections of ansa-FcdiOH-LNCs led to the growth inhibition of subcutaneous glioma. The last part of this work is devoted to the treatment of orthotopic glioma through various strategy of LNC administration (local or peripheral). The intra-carotid injection of FcdiOH-LNCs coated with the NFL-TBS peptide resulted in an improved survival time for some animals (5/12). The intracerebral sustained infusion of ferrocifen-loaded LNCs provoked severe toxicity and mortality. Finally, the repeated iv injections turned out to be an encouraging approach with a slight increase in the mean survival time (7%). Taken together, these results demonstrate the promising activity of the ferrocenyl complexes associated to OS LNCs for an alternative anticancer therapy approach.

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