Small molecule delivery using carbon nano-test-tubes Somlak Ittisanronnachai a , Hironori Orikasa a, * , Nobuhiro Inokuma a , Yoshihiro Uozu b , Takashi Kyotani a a Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku Sendai 980-8577, Japan b Mitsubishi Rayon Co. Ltd., 3816 Noborito, Tama-ku Kawasaki 214-0014, Japan ARTICLE INFO Article history: Received 3 March 2008 Accepted 9 May 2008 Available online 20 May 2008 ABSTRACT A dye, as a model for small molecular drug, was inserted into carbon nano test tubes (35 nm in diameter, 4.5 lm in length) synthesized using nanochannels of an anodic alumi- num oxide film as a template, and the open mouths of the test tubes were sealed by poly- styrene polymer. The resulting test tubes are dispersible in water, and the dye remains in the cavities because of the sealing. When the polymer-plug was dissolved by putting the test tubes into good solvents for polystyrene, the dye diffused out from the tube cavities. This study demonstrated the potential use of the test tubes as nano-sized carriers for drug and gene delivery. Ó 2008 Elsevier Ltd. All rights reserved. Carbon nanotubes (CNTs) have been extensively studied for their use as carriers for drug and gene delivery [1–3]. However, the size (both length and diameter) control of CNTs is inher- ently difficult, although the precise size control is indispens- able for such applications. On the other hand, the synthesis of tubular nano-carbons with controlled length and diameter has been developed by our group [4,5]. In this method, uni- form nanochannels of an anodic aluminum oxide (AAO) film are employed as a template. Recently, by using a similar technique, we have synthesized tubular nano-carbons with one end open but another end closed and found that this test-tube-like carbon (hereinafter referred to as carbon nano-test-tube (CNTT)) is dispersible in water without any post-modification [6]. Since the CNTT cavities are always accessible from outside through the open mouths, other materials can be easily introduced into the cavities. Indeed, we successfully filled the cavities with magnetic metal by electrochemical deposition [7,8]. It is thus reasonable to ex- pect that the insertion of drugs and proteins into the CNTTs is not a difficult task. However, if the CNTTs are used as drug capsules, sealing their open mouths is preferable, because their leakage and damage before reaching a target tissue should be avoided as much as possible. Here we insert a dye as a model for small molecular drug and seal the open ends of the CNTTs cavities with organic polymer plugs. We then simulate the drug release process by the removal of the poly- mer plugs and demonstrate promise for the use of CNTTs as drug or gene carriers. Fig. 1 shows the synthesis processes of the sealed and dye- containing CNTTs. At first, an AAO film with nanochannels (35 nm in diameter and 4.5 lm in length) was carbon-coated by acetylene CVD at 600 °C. This CVD treatment gives rise to uniform and continuous carbon coating over the whole sur- face of the AAO film (not only its external surface but also the inner wall of every nanochannel) so that the open end of each channel remains unclosed ever after the carbon depo- sition. Then a red-color dye (eosin-Y) as a model for a small molecular drug was inserted into the cavities of the carbon- coated AAO film. The sealing was carried out by keeping the open mouths of the carbon-coated AAO nanochannels in con- tact with a polymer film at a temperature higher than its glass transition temperature but less than its melting point. By detaching only the external polystyrene film from the car- bon-coated AAO film with the sealed polystyrene unchanged, the external carbon layer was exposed to the atmosphere and then only this layer was completely etched by oxygen plasma treatment. Upon the liberation from the AAO template by alkaline treatment, the sealed and dye-containing CNTTs were obtained as insoluble matter. More details of the synthe- sis are available in Supplementary material. In order to obtain polystyrene-sealed CNTTs like the ones illustrated in Fig. 1, we tried to optimize the polymer heating conditions using the carbon-coated AAO films without the dye introduction. The heating was conducted at various tem- peratures (140–200 °C) for different periods (1 min–24 h) and then the resulting polystyrene filled CNTTs were liberated from the AAO templates by the alkaline treatment. In each heating run, about fifty CNTTs were randomly observed with a transmission electron microscope (TEM) to examine the de- gree of the filling. Among these trials, we found that the 0008-6223/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.carbon.2008.05.013 * Corresponding author: Fax: +81 22 217 5626. E-mail address: orikasa@tagen.tohoku.ac.jp (H. Orikasa). CARBON 46 (2008) 1358 – 1367 1361