Carbon nanotubes (CNTs) are tube-like structures made from carbon atoms with diameters in nanometers. They are one of the most studied forms of carbon because they possess unique physicochemical properties that make them suitable for many biomedical applications.
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Their unique structure gives rise to an extraordinary combination of optical, mechanical, and electrical properties that are useful in drug and gene delivery systems, biomedical imaging, biosensors, tissue engineering, and antimicrobials.
Functionalization enables the extension of the functions of CNTs, but it has also been associated with toxicity. Here the properties of CNTs and their applications in the delivery of drugs and gene therapies, the development of biosensors, and imaging tools useful in diagnostics as well as tissue engineering are discussed. The toxicity of CNTs, and outlook on the place of CNTs in biomedicine are also provided.
Biomedical Applications
Carbon Nanotubes in the Delivery of Drugs and Genes
Many drug delivery systems based on CNTs have been developed to treat a wide range of diseases. In this area, CNT-based anticancer drugs have received a lot of attention due to the possibility of selective targeting and controlling the release of drugs. Selective targeting is possible because nanotubes can be made to target specific tumor receptors through functionalization, while the controlled release of drugs is desirable in tumor environments.
CNTs also have the advantage that they can form noncovalent bonds with molecules like aromatic compounds that cannot form covalent bonds. Many CNT-based drugs have been successfully designed using this model.
CNT use has also expanded to loading genetic material such as siRNAs and DNA applicable in gene therapy through gene silencing or gene delivery.
The transfection capabilities of CNTs are also notable, which allow them to enter cells irrespective of the kind of functionalization on their surfaces.
Laser stimulation technology can also leverage the photothermal properties of CNTs for the treatment of cancer.
Carbon Nanotubes in Diagnostics
Carbon Nanotubes in Biomedical Imaging
Biomedical imaging is a relatively new technology that can provide high-resolution imaging of the behavior of cells, tissues, organs, or the entire body.
CNTs can be altered to be subjected to various ways of biomedical imaging to study and improve their functions and responses to their environment due to their unique physical features. Also, because of CNTs’ high absorbance and metallic nanoparticles contaminants, photoacoustic imaging and magnetic resonance imaging can be used on CNTs.
CNT modification and the addition of other elements to their structure, like gold nanoparticles, can open new avenues for studying their behavior.
Carbon Nanotubes in Biosensors
Biosensors integrate biological recognition with chemical/physical transmission to detect biomolecules and are one of the important uses of CNTs. Their use as sensing elements in biosensors is due to their high surface area, superior electrical, mechanical, and electrochemical capabilities, and high exposure sensitivity to many biomolecules.
They enable the detection of biological structures at very low concentrations and hence are essential for ultrasensitive biosensing applications. Compared to more currently accessible sensing materials like silicon, CNT-based biosensors have unique benefits: a longer lifespan, faster response times, better sensitivity, and minimal surface fouling.
CNTs can also be built as DNA biosensors that are useful for systems-on-chip applications.
Carbon Nanotubes in Tissue Engineering and Regenerative Medicine
Tissue engineering and regenerative medicine are emerging medical methods to create artificial tissues for use in replacement grafts and tissue models for in vitro disease investigations and drug development. Here, CNTs can play a significant role by ensuring adequate mechanical, electrical, and biological properties of biomaterials, which is often quite challenging.
CNTs have been employed in tissue engineering for various purposes, including enhancing the mechanical and electrical properties of scaffolds, detecting the cell, microenvironments, cell tracking, and administration of appropriate chemical and biological agents.
Carbon Nanotubes-based Hydrogels
Hydrogels are 3D polymeric cross-linked edifices widely used in biomedical applications because of their high biocompatibility and low inflammatory responses but have limited intrinsic properties, which can be enhanced when coupled with CNT nanoparticles. These novel structures can bring innovative approaches to transdermal delivery patches by improving drug stability as well as giving more control over the rate of release.
Many biosensors that focus on glucose detection are also developed with CNT-based hydrogels.
Carbon Nanotubes as Antimicrobials
CNTs that have been functionalized can be used in vaccinations. CNTs have been demonstrated to activate innate immune system cells such as monocytes, macrophages, and dendritic cells. CNTs can activate many genes involved in monocyte response to infection or immunization.
Toxicity of Carbon Nanotubes
Toxicity has been reported in some CNT-based experiments. Some of the nanoparticles utilized in CNT functionalization may contribute to CNT toxicity, making the platform inappropriate for cellular life in some situations.
The amount and kind of metal impurities, the length and type of carbon nanotubes, the presence of surface functionalization and its type, and the presence of dispersant or surfactant in dispersion solution are all factors that contribute to CNT cytotoxicity. The mechanisms of toxicity are oxidative stress, cell membrane damage, or genotoxicity. Toxicity can be mitigated by controlling the amounts of reagents and modifications on CNTs.
Conclusions and Outlook
CNTs are bringing exciting new applications in nanobiotechnology. Their unique properties position them as suitable materials that address important challenges in biomedicine when used alone and in combination with other materials such as hydrogels. However, there are challenges of toxicity associated with functionalization. However, some can be overcome by carefully optimizing concentrations.
The characterization of CNTs in biological systems and a complete understanding of the cellular uptake, internalization, and changes in gene expression associated with the CNT toxicity have remained elusive. Understanding these mechanisms will be required for the future development of better CNTs for biomedical applications.
Proper documentation of their biological and environmental safety profiles will be required to encourage full adoption and large-scale use.
References and Further Reading
Alshehri, R., Ilyas, A.M., Hasan, A., Arnaout, A., Ahmed, F., Memic, A. (2016). Carbon Nanotubes in Biomedical Applications: Factors, Mechanisms, and Remedies of Toxicity. Journal of Medical Chemistry, 59, pp8149–8167. https://doi.org/10.1021/acs.jmedchem.5b01770
Lamberti, M., Pedata, P., Sannolo, N., Porto, S., De Rosa, A., Caraglia, M. (2015). Carbon nanotubes: Properties, biomedical applications, advantages and risks in patients and occupationally-exposed workers. International Journal of Immunopathology and Pharmacology, 28, pp.4–13. https://doi.org/10.1177/0394632015572559
Pondman, K.M., Sobik, M., Nayak, A., Tsolaki, A.G., Jäkel, A., Flahaut, E., Hampel, S., ten Haken, B., Sim, R.B., Kishore, U. (2014). Complement activation by carbon nanotubes and its influence on the phagocytosis and cytokine response by macrophages. Nanomedicine: Nanotechnology, Biology and Medicine, 10, pp.1287–1299. https://doi.org/10.1016/j.nano.2014.02.010
Simon, J., Flahaut, E., Golzio, M. (2019). Overview of Carbon Nanotubes for Biomedical Applications. Materials (Basel) 12, pp.624. https://doi.org/10.3390/ma12040624
Zhou, Y., Fang, Y., Ramasamy, R.P. (2019). Noncovalent Functionalization of Carbon Nanotubes for Electrochemical Biosensor Development. Sensors 19, pp.392. https://doi.org/10.3390/s19020392
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