Multimodal functionalized carbon nanotube/iron oxide nanoparticle hybrids for imaging and therapeutic applications – NANOTHER

The continuous growing of Nanotechnology has brought to challenging innovations in medicine revolutionizing the field of therapy, in particular the delivery of biologically active compounds and the local treatments of diseases. The main input of today’s Nanotechnology in the biomedical field is that it allows real progress to achieve temporal and spatial site-specific drug delivery, local therapy, and imaging.
In this context, the NANOTHER project will focus on the design, the synthesis and the therapeutic applications of multifunctional functionalized carbon nanotube/iron oxide nanoparticle conjugates. These hybrids will serve as multimodal imaging and therapy platforms. Indeed, the association of the magnetic properties of iron oxide nanoparticles (NPs) to the characteristics of carbon nanotubes (CNTs) is an innovative approach that will allow opening new possibilities in terms of imaging, activation and spatial manipulation in vivo via magnetic stimulation.
CNTs are promising for biomedical applications as they are capable of crossing many biological and biophysical barriers. Moreover, the high aspect ratio and large surface area allows functionalizing CNTs with multiple copies of different molecules of interest.
In the NANOTHER project, we propose to prepare magnetic CNTs by filling the empty internal cavity of the nanotubes or by decoration of their outer surface with magnetic materials such as iron oxide NPs. CNTs possessing magnetic properties will offer the potential for imaging, as well as hyperthermia. The iron oxide NPs bring additional functions to CNTs for imaging, as they are used as negative contrast agent for magnetic resonance imaging (MRI), and for therapy with magnetically-induced hyperthermia. Due to their optical properties, CNTs can absorb near-infrared (NIR) light and convert the energy into heat. This property will be also used in the NANOTHER project for hyperthermia treatments as an alternative to magnetically-induced thermal ablation. The required quantity of CNTs to induce hyperthermia by IR irradiation is lower by comparison with magnetic iron oxide NPs activated by high frequency magnetic field. Therefore, the double therapy by exploiting one single nano-object certainly offers several advantages on the treatment of cancer.
The CNT/NP complexes will be used for imaging by derivatizing either the CNTs or the NPs with dendrimers chelating different radionuclides. The choice of the dendritic molecules is motivated by the fact that they are discrete and monodisperse entities which relevant characteristics (e.g. size, hydrophilicity, molecular weight, biocompatibility) can be finely tuned as a function of their generation. To improve the thermal ablation effect and to provide molecular-level contrast, we plan to further functionalize the CNT/NP complexes with targeting agents. The development of target-specific MRI contrast agents (CAs), directed to defined molecular markers, could dramatically improve the imaging of a specific disease, due to the accumulation of MRI contrast agent at the region of interest. Alternatively, the magnetic properties of the CNT/NP conjugates will be also exploited to concentrate the CNT/NP hybrids at the site of disease by applying a magnetic field.
The CNTs will be detectable by MRI for biodistribution studies. In addition, we plan to induce cytotoxic effects by magnetic manipulation. It will be possible to improve internalization of the nano-constructs by oscillating magnetic forces. We can also envisage an intracellular activation by low frequency alternating magnetic field via possible rotation of CNTs to stress intracellular target by application of a magnetic field. The therapeutic potential of such innovative multimodal hybrids will be applied in vivo to two cancer models: neuroblastoma and melanoma.