Bioconjugated Iron-Filled Carbon Nanotubes As Cancer Theranostics Agents

Magnetic nanoparticles (MNPs) and carbon nanotubes (CNTs) have emerged as two new classes of nanomaterials for simultaneous diagnostics and treatment (theranostics) of cancer. On one hand, MNPs can act as magnetic resonance imaging (MRI) contrast agents, magnetically-driven drug delivery cargoes, filtrations and selective separations of biological entities agents and magnetic fluid hyperthermia (MFH) treatments.^[1] On the other hand, CNTs have been used against cancer as intracellular carriers for biologically relevant species^[2] thanks to their large surface area and their faculty to penetrate cells or as infrared hyperthermia agents^[3], among other possibilities.^[4]

In order to combine the advantages of both parts, we synthesized in our group a hybrid composed of metallic iron nanoparticles filled in multiwall carbon nanotubes (Fe@CNTs) bioconjugated to the monoclonal antibody (mAb) Cetuximab. CNTs graphitic layers offers a protection against oxidation of iron nanoparticles, keeping them in more magnetically active phases whereas mAb targets epidermal growth factor receptor (EGFR) overexpressing A431 cancer cells. In a pilot study, we showed the in vitro efficiency of Fe@CNTs in selective targeting and elimination of A431 cells over control cell lines via magnetic filtration and hyperthermia.^[5] We then studied in detail various Fe@CNTs possessing different phases of iron, in order to correlate their structural and magnetic properties onto their biological performances.^[6]

In parallel we developed seminal work^[7]led by our team about H-bonded supramolecular polymer (SMP) able to wrap around CNTs to exploit the potential of our Fe@CNTs as a non-covalent scaffold. We thus synthesized new pegylated H-bonded supramolecular polymers able to solubilize Fe@CNTs in aqueous media. Moreover, this polymer-CNTs nano-assembly shows interesting properties of reversible wrapping and un-wrapping under thermal stimulus, and is envisaged to be used for simultaneous MFH and triggered drug delivery treatments.

References:

[1]       V. I. Shubayev, T. R. Pisanic, S. Jin, Adv. Drug Deliv. Rev. 2009, 61, 467–77.

[2]       H. Dai, Acc. Chem. Res. 2002, 35, 1035–44.

[3]       R. Singh, S. V Torti, Adv. Drug Deliv. Rev. 2013, 1–16.

[4]       C. Fabbro, H. Ali-Boucetta, T. Da Ros, K. Kostarelos, A. Bianco, M. Prato, Chem. Commun. 2012, 48, 3911–26.

[5]       R. Marega, F. De Leo, F. Pineux, J. Sgrignani, A. Magistrato, A. D. Naik, Y. Garcia, L. Flamant, C. Michiels, D. Bonifazi, Adv. Funct. Mater. 2013, 23, 3173–3184.

[6]       F. Pineux, M. Riccardo, A. Stopin, A. La Torre, Y. Garcia, C. Michiels, D. Bonifazi, Manuscript in preparation

[7]       A. Llanes-Pallas, K. Yoosaf, H. Traboulsi, J. Mohanraj, T. Seldrum, J. Dumont, A. Minoia, R. Lazzaroni, N. Armaroli, D. Bonifazi, J. Am. Chem. Soc. 2011, 133, 15412–24.

Figure : Scheme of an iron-filled Carbon Nanotube conjugated with a monoclonal antibody (Fe@CNT-mAb), wrapped with our supramolecular polymer.