Smart Engineering of Carbon Nanotubes: A promising Way to Designing Efficient and Versatile Drug Delivery Systems

The development of new and efficient Drug Delivery Systems (DDS) is of fundamental importance to improve the pharmacological profiles of many classes of therapeutic molecules. Among the different types of drug delivery systems, carbon nanotubes (CNT) have emerged in recent years as promising materials due to their peculiar structures and properties. In particular, properly functionalized CNTs display low toxicity and great ability to easily penetrate the cellular membrane, thus allowing their exploitation as DDS.1 Due to a large variety of functionalization protocols available for their surface decoration,2 CNTs can be easily functionalized with biologically active molecules as well as molecular dyes for their monitoring in the biological medium. The development of new functionalization protocols able to impart multimodality to nanomaterials finally represents a challenging research area. Indeed, the possibility to bring different molecular moieties at the nanomaterial surface, while maintaining a full control on their relative loading, holds unique promises in nanotechnologies applied to biological systems. In particular, the incorporation of functionalities containing cleavable bonds (under appropriate chemical and/or biological settings) represents a step-forward towards the smart engineering of these nanostructures. A controlled molecular exchange at the CNT surface can offer an unique strategy to the controlled release of specific guest molecules initially linked to the surface of the nanomaterial carrier (CNT). Starting from a valuable protocol developed by us for the controlled single-step homo- and hetero-functionalization of CNT sidewalls through "click" chemistry,3 we have designed and synthesized a simple organic linker joining a "cleavable" disulfide moiety and a "clickable" terminal acetylene group. The functionalization scheme allows to impart multimodality (i.e. multifunctionality) to 1D carbon nanostructures while they operate as nanocarriers for biological probes. The developed functionalization strategy allows a direct estimation of the CNT-covalently grafted biomolecule loading, while an appropriate hetero-decoration of the nanomaterial with a selected fluorescence dye generates an optically traceable bioconjugate.4 Taking advantage of the as-developed multimodal CNTs functionalization protocol, we have designed and synthesized new DDS with significant anticancer activity, as assessed by in vitro and in vivo tests.5,6