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The emerging field of nanotube biotechnology

Key Points

  • Nanoparticles are being developed for a host of biomedical and biotechnological applications, including drug delivery, enzyme immobilization and DNA transfection. Spherical nanoparticles are typically used for such applications, but this only reflects the fact that spheres are easier to make than other shapes.

  • Micro- and nanotubes — structures that resemble tiny drinking straws — are alternatives, and might offer advantages over spherical nanoparticles for some applications.

  • Micro- and nanotube technologies reviewed in this paper are as follows: Microtubes based on self-assembling lipids; fullerene carbon nanotubes; nanotubes based on cyclic peptides; and template-synthesized nanotubes.

  • Cyclic peptide nanotubes can act as a new type of antibiotic against bacterial pathogens.

  • Fullerene nanotubes can be used as ultra-high-resolution atomic-force microscopy tips.

  • The template method is the most versatile approach for making nanotubes because the nanotubes obtained can be composed of any desired material, including polymers, inorganic materials such as semiconductors or silica, metals and carbons. The template method can also be used to prepare concentric tubular nanostructures where a tube of one material surrounds a tube of a second.

  • It is easy to chemically functionalize the surfaces of template-synthesized nanotubes, and different functional groups can be attached to the inner versus. outer surfaces of the tubes.

  • Biomolecules, such as enzymes, antibodies, and DNA chains, can be attached to the nanotube surfaces to make biofunctionalized nanotubes.

  • Template-synthesized nanotubes can be used as smart nanophase extraction agents to remove, for example, drug molecules from solution.

  • Template-synthesized nanotube membranes offer new approaches for doing bioseparations, such as enantioseparations of drug molecules.

Abstract

Nanoparticles are being developed for a host of biomedical and biotechnological applications, including drug delivery, enzyme immobilization and DNA transfection. Spherical nanoparticles are typically used for such applications, which reflects the fact that spheres are easier to make than other shapes. Micro- and nanotubes — structures that resemble tiny drinking straws — are alternatives that might offer advantages over spherical nanoparticles for some applications. This article discusses four approaches for making micro- and nanotubes, and reviews the current status of efforts to develop biomedical and biotechnological applications of these tubular structures.

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Figure 1: Scanning electron micrograph of an array of template-synthesized carbon nanotubes.
Figure 2: Typical lipids used to make self-assembling lipid microtubes.
Figure 3: Transmission electron micrograph of fullerene carbon nanotubes.
Figure 4: Cyclic peptide nanotubes.
Figure 5: The α-haemolysin protein channel, an example of a naturally occuring nanotube.
Figure 6: Scanning electron micrographs.
Figure 7: Schematic of the procedure used to attach different chemical functional groups to the inner versus outer surfaces of template-synthesized nanotubes.
Figure 8: Enantioseparations.

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Acknowledgements

This work was supported by the National Science Foundation, (Nanoscale Interdisciplinary Research Teams for Biomedical Nanotube Technology) the Office of Naval Research and the UF Engineering Research Center for Particle Science and Technology. We gratefully acknowledge our collaborator H. Soderlund for contributions to the antibody research projects.

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Correspondence to Charles R. Martin.

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DATABASES

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α-haemolysin

Online Mendelian Inheritance in Man

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FURTHER INFORMATION

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Glossary

BIOSENSOR

A chemical or electronic device that, when immersed in a solution (for example, a water sample or an air sample), binds a particular chemical component of the solution and produces an electronic signal that is proportional to the concentration of the component in the solution.

CHIRAL

The property of a molecule that has no plane of symmetry such that it cannot be superimposed on its mirror image. This typically occurs when the molecule has at least one carbon atom that is bonded to four different groups. A chiral molecule is like a person's hands: the right and left hands appear the same, but they are, in fact, non-superimposable mirror images of each other.

D- VERSUS L- AMINO ACIDS

The amino acids that make up proteins are CHIRAL (see above). The two forms are called enantiomers. One enantiomer is called the D-enantiomer of the amino acid and the other is called the L-enantiomer. These terms come from the direction that a solution of the enantiomer rotates the plane of plane-polarized right.

HYDROGEN BONDING

A strong type of dipole–dipole interaction that can occur between two molecules. One molecule must have a hydrogen atom bound to a very electronegative atom, such as oxygen, nitrogen or fluorine; the other must have a lone pair of electrons on such an atom.

NANOWIRE

A wire of a material (for example, a metal), the diameter of which is less than 100 nm.

IN-PORE POLYMERIZATION

A polymerization process that takes place within the pores of one of the template membranes, which is used to make a polymeric nanowire or nanotube.

ELECTROLESS DEPOSITION

A method for coating metal films onto non-metallic surfaces, such as plastics. It involves reducing an ionic form of the metal at the surface using a chemical reducing agent.

SOL–GEL CHEMISTRY

A versatile route for synthesizing typically inorganic materials, such as semiconductors and silica. This method involves hydrolysis of a molecular precursor followed by thermal treatment, typically in air.

LIPOPHILIC

The propensity of a molecule to dissolve in a non-polar, oil-like solvent. This term originates from the fact that naturally occurring lipid molecules have this propensity.

RACEMIC MIXTURE

An equimolar mixture of the two enantiomers of a chiral molecule.

ENANTIOSEPARATIONS

The separation of one enantiomer of a chiral molecule from the other. This is an important issue in drug development because drug molecules are typically chiral, and only one of the enantiomers tends to be efficacious.

STEREOISOMERS

Isomers are chemical compounds that have the same molecular formula but different molecular structures (structural isomers) or different arrangements of atoms in space (stereoisomers).

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Martin, C., Kohli, P. The emerging field of nanotube biotechnology. Nat Rev Drug Discov 2, 29–37 (2003). https://doi.org/10.1038/nrd988

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