Functionalized Carbon Nanotubes in Drug Design and Discovery

Maurizio Prato obtained his Laurea degree in chemistry in 1978 from the University of Padova, Italy, where he was appointed Assistant Professor in 1983. He moved to Trieste as an Associate Professor in 1992. He was therefore promoted to Full Professor in 2000. He spent a postdoctoral year in 1986–1987 at Yale University, was Visiting Scientist at the University of California, Santa Barbara, in 1991–1992, and was Professeur Invité at the Ecole Normale Supérieure in Paris, France, in July 2002. His research interests focus on the functionalization chemistry of fullerenes and carbon nanotubes for applications in materials science and medicinal chemistry and on the synthesis of biologically active substances. His scientific contributions have been recognized by national awards, which include Federchimica Prize (1995, Association of Italian Industries) and the National Prize for Research (2002, Italian Chemical Society).

Kostas Kostarelos is Chair of Nanomedicine at The School of Pharmacy, University of London and a Fellow of the Royal Society of Medicine (FRSM) and the Institute of Nanotechnology (FIoN). He read chemistry at the University of Leeds, UK, and obtained his Diploma and PhD in Chemical Engineering from Imperial College London. His previous academic appointments include Deputy Director, Imperial College Genetic Therapies Centre, Imperial College London, UK; Assistant Professor of Genetic Medicine & Chemical Engineering in Medicine, Cornell University Weill Medical College, NY, USA; Manager, Bioengineering Core, Belfer Gene Therapy Center, Cornell University Weill Medical College, NY, USA; Instructor, Pulmonary & Critical Care Medicine, New York-Presbyterian Hospital, NY, USA. He is the Senior Editor of the journal Nanomedicine and a Senior Founding Member of the American Academy of Nanomedicine (Washington, DC, USA).

Alberto Bianco received his Laurea degree in Chemistry in 1992 and his PhD in 1995 from the University of Padova (Italy), under the supervision of Professor Claudio Toniolo, working on fullerene-based amino acids and peptides. As a visiting scientist, he worked at the University of Lausanne during 1992 (with Professor Manfred Mutter), at the University of Tübingen in 1996–1997 (with Professor Günther Jung, as an Alexander von Humboldt fellow), and at the University of Padova in 1997–1998 (with Professor Gianfranco Scorrano). He currently is a Research Director at CNRS in Strasbourg (France). His research interests focus on the development of carbon-based nanomaterials (carbon nanotubes and fullerenes) and their use as therapeutic vectors; the applications of functionalized carbon nanotubes and fullerenes in nanomedicine; the synthesis of peptidomimetics containing fullero-amino acids as new ligands for immunotherapy; and the organic and combinatorial solid phase synthesis and characterization of the molecules on the solid support by HRMAS NMR. He is member of the American Chemical Society, the French Group of Peptides and Proteins, and the European Peptide Society.

Carbon nanotubes (CNTs) have been proposed and actively explored as multipurpose innovative carriers for drug delivery and diagnostic applications. Their versatile physicochemical features enable the covalent and noncovalent introduction of several pharmaceutically relevant entities and allow for rational design of novel candidate nanoscale constructs for drug development. CNTs can be functionalized with different functional groups to carry simultaneously several moieties for targeting, imaging, and therapy. Among the most interesting examples of such multimodal CNT constructs described in this Account is one carrying a fluorescein probe together with the antifungal drug amphotericin B or fluorescein and the antitumor agent methotrexate. The biological action of the drug in these cases is retained or, as in the case of amphotericin B constructs, enhanced, while CNTs are able to reduce the unwanted toxicity of the drug administered alone. Ammonium-functionalized CNTs can also be considered very promising vectors for gene-encoding nucleic acids. Indeed, we have formed stable complexes between cationic CNTs and plasmid DNA and demonstrated the enhancement of the gene therapeutic capacity in comparison to DNA alone. On the other hand, CNTs conjugated with antigenic peptides can be developed as a new and effective system for synthetic vaccine applications. What makes CNTs quite unique is their ability, first shown by our groups in 2004, to passively cross membranes of many different types of cells following a translocation mechanism that has been termed the nanoneedle mechanism. In that way, CNTs open innumerable possibilities for future drug discovery based on intracellular targets that have been hard to reach until today. Moreover, adequately functionalized CNTs as those shown in this Account can be rapidly eliminated from the body following systemic administration offering further encouragment for their development. CNT excretion rates and accumulation in organs and any reactivity with the immune system will determine the CNT safety profile and, consequently, any further pharmaceutical development. Caution is advised about the need for systematic data on the long-term fate of these very interesting and versatile nano-objects in correlation with the type of CNT material used. CNTs are gradually plyaing a bigger and more important role in the emerging field of nanomedicine; however, we need to guarantee that the great opportunities they offer will be translated into feasible and safe constructs to be included in drug discovery and development pipelines.