ABSTRACT

Nanotechnology is an interdisciplinary research effort bridging many scientific fields from physics and chemistry to engineering, biology, and medicine. The result of such interconnections is holding great potential for the early detection, diagnosis, and personalized treatment of disease. The nanoscale range at which nanosystems operate, i.e., one-thousandth smaller than a human cell, can offer facile transport across the human body and intracellular interactions with many cell components that would otherwise be inaccessible. Imaging for early detection and diagnosis of diseases using newly emerged nanoparticles such as quantum dots (QDs) [21], carbon nanotubes (CNTs) [19], nanoshells [10], paramagnetic nanoparticles [34], and others [6, 9] have been an area of interest over the last few years.Carbon nanotubes are a type of nanomaterial that offers unique intrinsic properties that make them very interesting candidates as imaging contrast agents. Their identification in the early 1990s [12] and their further biomedical development [18] opened a new era in the development of novel delivery systems for therapeutics and diagnostics. Carbon nanotubes are mainly classified as single-walled (SWNTs)

or multiwalled (MWNTs) according to the number of concentric layers of graphitic sheets rolled into cylindrical structures. The high aspect ratio of CNT offers great advantages over other nanoparticle types, since the high surface area provides multiple attachment sites for drugs, targeting ligands, and imaging probes. Advancements achieved in filling CNT with small molecules or other nanomaterials also indicate an opportunity to use them as imaging probes in vivo [11, 30, 35]. One of the main disadvantages of CNT is their hydrophobicity, so advances in solubilization and dispersion methodologies, including chemical functionalization of the CNT surface [4] or coating with amphiphilic molecules such as PEGylated phospholipids or polymers [13], have been an essential breakthrough to allow exploitation of the biomedical applications of CNT. Recently, successful studies in our laboratories as well as others have reported that CNT can translocate into cells using several analytical techniques, including optical microscopy, micro-Raman spectroscopy, single-particle tracking (SPT), transmission electron microscopy (TEM), flow cytometry, and fluorescence microscopy. Moreover, proof-of-concept studies have established that CNT can act as delivery systems for drugs (methotrexate, amphotericin) [26, 37], antigens, and genes (plasmid DNA, siRNA) [14, 32] into prokaryotic and mammalian cells with minimal cytotoxicity both in vitro [3, 5] and in vivo [2, 27, 40]. This indeed allows for using CNTs not only as multimodal imaging probes but also as theranostic devices.