Carbon nanotubes delivery

An improved delivery scheme for intracellular tracking and anticancer therapy uses a novel double functionalization of a carbon nanotube delivery system containing antisense oligodeoxynucleotides as a therapeutic gene and CdTe QDs as fluorescent labeling probes via electrostatically layer-by-layer assembling [39]. 

Gao L, Nie L, Wang T et al (2006) Carbon nanotube delivery of the GFP gene into mammalian cells. Chembiochem 7 239-242... 

Feazell, R.P. et al. (2007) Soluble single-walled carbon nanotubes as longboat delivery systems for platinum(IV) anticancer drug design. Journal of the American Chemical Society, 129 (27), 8438-8439. 

Lacerda, L. et al. (2006) Carbon nanotubes as nanomedicines from toxicology to pharmacology. Advanced Drug Delivery Reviews, 58 (14), 1460-1470. 

A. Bianco, K. Kostarelos, and M. Prato, Applications of carbon nanotubes in drug delivery, Curr. Opin. Chem. Biol., 9 (2005) 674—679. 

G. Pastorin, K. Kostarelos, M. Prato, and A. Bianco, Functionalized carbon nanotubes Towards the delivery of therapeutic molecules, /. Biomed. Nano-technol., 1 (2005) 133-142. 

The same group reported the simultaneous radiolabeling (with DOTA-anchored 4Cu) and fluorescence studies, coupled with biodistribution in vivo and in vitro (92). It is believed that appropriately functionalized SWNTs can efficiently reach tumor tissues in mice with no apparent toxicity (159). Furthermore, water-solubilised carbon nanotubes are nontoxic when taken up by cells even in high concentration (92). These studies have been complemented by the recent PET imaging of water-soluble 86Y labelled carbon nanotubes in vivo (mice) (160,161), to explore the potential usefulness of carbon nanocarriers as scaffolds for drug delivery. The tissue biodistribution and pharmacokinetics of model DOTA functionalized nanotubes have been explored in vivo (mouse model). MicroPET images indicated accumulation of activity mainly in the kidney, liver, spleen, and to a much less... 

Keywords Carbon nanotubes, Functionalization, Drag Delivery, Gene transfer, Health, Biodistribution... 

This chapter will describe the potential of carbon nanotubes in biomedicine. It will illustrate the methodologies to render nanotubes biocompatible, the studies on their cell uptake, their application in vaccine delivery, their interaction with nucleic acids and their impact on health. 

Carbon Nanotubes and Immunological Response 2.4.1 Carbon Nanotubes for Peptide Delivery... 

In recent years, CNTs have been receiving considerable attention because of their potential use in biomedical applications. Solubility of CNTs in aqueous media is a fundamental prerequisite to increase their biocompatibility. For this purpose several methods of dispersion and solubilisation have been developed leading to chemically modified CNTs (see Paragraph 2). The modification of carbon nanotubes also provides multiple sites for the attachment of several kinds of molecules, making functionalised CNTs a promising alternative for the delivery of therapeutic compounds. 

Cai D, Mataraza JM, Qin ZH, Huang ZP, Huang JY, Chiles TC, Carnahan D, Kempa K, Ren ZF (2005) Highly efficient molecular delivery into mammalian cells using carbon nanotube spearing. Nat. Methods 2 449 154. 

Kam NWS, Liu Z, Dai HJ (2005a) Functionalization of carbon nanotubes via cleavable disulfide bonds for efficient intracellular delivery of siRNA and potent gene silencing. J. Am. Chem. Soc. 127 12492-12493. 

Liu Y, Wu DC, Zhang WD, Jiang X, He CB, Chung TS, Goh SH, Leong KW (2005) Polyethylenimine-grafted multiwalled carbon nanotubes for secure noncovalent immobilization and efficient delivery of DNA. Angew. Chem. Int. Ed. 44 4782 4785. 

Liu Z, Sun X, Nakayama-Ratchford N, Dai H (2007a) Supramolecular Chemistry on Water-Soluble Carbon Nanotubes for Drug Loading and Delivery. ACS Nano 1 50-56. 

Liu Z, Winters M, Holodniy M, Dai HJ (2007b) siRNA delivery into human T cells and primary cells with carbon-nanotube transporters. Angew. Chem. Int. Ed. 46 2023-2027. 

Pantarotto D, Singh R, McCarthy D, Erhardt M, Briand JP, Prato M, Kostarelos K, Bianco A (2004b) Functionalized carbon nanotubes for plasmid DNA gene delivery. Angew. Chem. Int. Ed. 43 5242-5246. 

Pastorin G, Wu W, Wieckowski S, Briand JP, Kostarelos K, Prato M, Bianco A (2006) Double functionalisation of carbon nanotubes for multimodal drug delivery. Chem. Commun. 1182-1184. 

Rojas-Chapana J, Troszczynska J, Firkowska I, Morsczeck C, Giersig M (2005) Multi-walled carbon nanotubes for plasmid delivery into Escherichia coli cells. Lab Chip 5 536-539. 

Simon F, Peterlik H, Pfeiffer R, Bemardi J, Kuzmany H (2007) Fullerene release from the inside of carbon nanotubes A possible route toward drug delivery. Chem. Phys. Lett. 445 288-292. 

Singh R, Pantarotto D, McCarthy D, Chaloin O, Hoebeke J, Partidos CD, Briand JP, Prato M, Bianco A, Kostarelos K (2005) Binding and condensation of plasmid DNA onto functionalized carbon nanotubes Toward the construction of nanotube-based gene delivery vectors. J. Am. Chem. Soc. 127 4388 4396. 

Yinghuai Z, Peng AT, Carpenter K, Maguire JA, Hosmane NS, Takagaki M (2005) Substituted carborane-appended water-soluble single-wall carbon nanotubes New approach to boron neutron capture therapy drug delivery. J. Am. Chem. Soc. 127 9875-9880. 

CNTs can also be encapsulated with DNA molecules. As shown in Fig. 9.1, a DNA molecule could be spontaneously inserted into a SWNT in a water solution via molecular dynamics simulation (Gao et al., 2003). The van der Waals and hydrophobic forces were very key factors for the insertion process, with the former playing a more dominant role in the course of DNA entering into the hole of CNT. Experiment also confirmed that Pt-labeled DNA molecules can be encapsulated into multi-walled carbon nanotubes in water solution at 400 K and 3 Bar as shown in Fig. 9.2 (Cui et al., 2004). The CNTs filled with DNA molecules have potential in applications such as gene delivery system, and electronic sequencing, nanomotor, etc. 

As with fullerenes, carbon nanotubes are also hydrophobic and must be made soluble for suspension in aqueous media. Nanotubes are commonly functionalized to make them water soluble although they can also be non-covalently wrapped with polymers, polysaccharides, surfactants, and DNA to aid in solubilization (Casey et al., 2005 Kam et al., 2005 Sinani et al., 2005 Torti et al., 2007). Functionalization usually begins by formation of carboxylic acid groups on the exterior of the nanotubes by oxidative treatments such as sonication in acids, followed by secondary chemical reactions to attach functional molecules to the carboxyl groups. For example, polyethylene glycol has been attached to SWNT to aid in solubility (Zhao et al., 2005). DNA has also been added onto SWNT for efficient delivery into cells (Kam et al., 2005). 

---