MTG

Microrobots Targeting Glioblastoma (MTG)

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Understand the Glioblastoma, to allow its destruction with magnetic microbots loaded with NFL peptide…

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Keywords: dfolio, projects, research, activities, microrobot

Microbots to kill Glioblastoma

Glioblastoma multiform (GBM) is the most frequent and aggressive cancer of the nervous system (5 cases/year for 100.000 habitants1). The first line chemotherapy includes alkylating agent Temozolomide concomitantly with radiotherapy (Stupp protocol), but the average survival is limited to 15 months. Classical anti-cancer therapies show poor efficacy for GBM because of their low specificity and toxic effect on healthy cells. The MINT unit, headed by Dr. Joël Eyer, has identified a peptide2 (NFL peptide), which :

  1. enters specifically in all GBM tested (rat, mouse and human),
  2. targets the entry of lipid nanocaspules into GBM cells,
  3. inhibits GBM cell division in vitro and in vivo on rats with a GBM tumor implanted in the brain [1][3].

Our goal is then to mix the NFL peptide with magnetic particle to design a magnetic microrobot. This strategy provides a minimally invasive surgery together with an optimized concentration and delivery of therapeutic principle to the tumor, consequently lowering the toxic effects on healthy cells. We will synergize our expertise to functionalize microrobots with the NFL peptide in order to develop Microrobots Targeting Glioblastoma (MTG). These MTG filled with a fluorochrome will be tested in vitro for their capacity to target GBM versus healthy cells. Then, they will be injected intravenously in rats bearing a GBM tumor to evaluate their capacity to cross the blood-brain-barrier, to target the tumor, and to reduce its development when filled with cytotoxic products.

References

[1]
Balzeau J., Peterson A., and Eyer J., “The vimentin-tubulin binding site peptide (vim-TBS. 58-81) crosses the plasma membrane and enters the nuclei of human glioma cells,” International journal of pharmaceutics, vol. 423, no. 1, pp. 77–83, 2012. doi:10.1016/j.ijpharm.2011.04.067
[2]
Berges R., Balzeau J., Peterson A. C., and Eyer J., “A tubulin binding peptide targets glioma cells disrupting their microtubules, blocking migration, and inducing apoptosis,” Molecular Therapy, vol. 20, no. 7, pp. 1367–1377, 2012. doi:10.1038/mt.2012.45
[3]
Bocquet A., Berges R., Frank R., Robert P., Peterson A. C., and Eyer J., “Neurofilaments bind tubulin and modulate its polymerization,” Journal of Neuroscience, vol. 29, no. 35, pp. 11043–11054, 2009. doi:10.1523/JNEUROSCI.1924-09.2009

Footnotes

  1. Source: Institut National du Cancer http://www.e-cancer.fr↩︎

  2. Peptides are short chains of amino acids, see also https://en.wikipedia.org/wiki/Peptide↩︎

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