Brain tumour targeting strategies via coated ferrociphenol lipid nanocapsules

In this study, a new active targeting strategy to favour ferrociphenol (FcdiOH) internalisation into brain tumour cells was developed by the use of lipid nanocapsules (LNCs) coated with a cell-internalising peptide (NFL-TBS.40–63 peptide) that interacts with tubulin-binding sites. In comparison, OX26 murine monoclonal antibodies (OX26-MAb) targeting transferrin receptors were also inserted onto the LNC surface. The incorporation of OX26 or peptide did not influence the in vitro antiproliferative effect of FcdiOH–LNCs on the 9L cells since their IC50 values were found in the same range. In vivo, intracerebral administration of OX26–FcdiOH–LNCs or peptide–FcdiOH–LNCs by convection enhanced delivery did not enhance the animal median survival time in comparison with untreated rats (25 days). Interestingly, intra-carotid treatment with peptide–FcdiOH–LNCs led to an ameliorated survival time of treated rats with the presence of animals surviving until days 35, 40 and 44. Such results were not obtained with OX26-MAbs, demonstrating the benefit of NFL-TBS.40–63 peptide as an active ligand for peripheral drug delivery to the brain tumours.

The cell- internalising ability of the NFL-TBS.40-63 peptide has been exploited and combined to lipid nanocapsules (LNCs) in order to develop an active brain tumour targeting carrier. 9L glioma-bearing rats treated with an intra-carotid injection of the ferrociphenol anticancer drug trapped into the peptide-LNCs showed marked survival time increase compared to that of the control group. These results emphasise the great interest of using a cell-penetrating peptide such as the NFL-TBS.40-63 peptide in the glioma therapy.Figure optionsDownload high-quality image (93 K)Download as PowerPoint slide