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WIREs Nanomed Nanobiotechnol
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Therapeutic applications of carbon nanotubes: opportunities and challenges

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Based on their physicochemical properties that allow efficient functionalization with biomolecules and cellular membrane translocation, as well as on their applications in Raman and near‐infrared fluorescence imaging, carbon nanotubes (CNTs) have been proposed as viable candidates for developing therapeutic platforms that ensure targeting of tumor cells without affecting healthy cells. This article reviews the research on toxicological effects of CNTs on host cells, as well as their pharmacological profiles on cancer cells. The potential impact of this approach is discussed along with some potential pitfalls that will need to be overcome when therapeutic implementation CNTs are considered. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials
(a) A diagram of a eukaryotic cell mitotic spindle configuration. Three distinct types of microtubules involved in spindle formation are observed: (1) kinetochore microtubules that bind with their minus end at the centrosome and then can attach to the kinetochore of the sister chromatids using their plus end; (2) interpolar microtubules that bind with their minus end at the centrosome and then overlap in the mid‐zone region of the mitotic spindle; and (3) astral microtubules that bind with their minus end at the centrosome, while their plus ends grow outward toward cell cortex. The molecular motors involved in the mitotic spindle assembly (i.e., the main players of the cell division) are dynein, Eg5, kinesin 14, and kinesins 4 and 10. The motors move on their microtubule tracks using ATP hydrolysis and provide directional forces required for proper spindle formation and alignment. Microtubules and mitotic molecular motors work in concert to achieve normal cell division. (b) Following carbon nanotube (CNT) exposure, nanomaterials can interact with the centrosomes, microtubules, and the mitotic molecular motors to inhibit proper spindle formation. Further, CNTs can be bound and encapsulated by the cytoskeletal microtubules leading to biohybrid assembly formation. Lack of association of the mitotic molecular motors with the CNTs–microtubule biohybrids could mis‐position the centrosomes and thus induce genotoxicity and tumorigenesis.
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(a) Three‐dimensional reconstruction of the multipolar mitotic spindle of human lung BEAS‐2B epithelial cells incubated with single‐walled carbon nanotubes (SWCNTs) using serial optical sections of 0.1 µm. The DNA is shown in blue, tubulin is in red, centrosomes are in green, and the nanotubes are shown in black. The three‐spindle poles are indicated by the white arrows. The reconstructed image shows nanotubes inside the cell and in association with each centrosome leading to centrosome fragmentation. Nanotubes are also integrated with the microtubules and the DNA suggesting major perturbations in cell division. (Reprinted with permission from Ref . Copyright 2012 Elsevier). (b) Confocal microscopy projection images of aberrant mitotic spindles in HeLa cells treated with multiwalled carbon nanotubes (MWCNTs). Aberrations in the organization of the spindle microtubules (red channel) and chromosomal distribution (blue channel) are shown in contrast with the bipolar spindle of the control cell. Several abnormalities in the spindle formation have been observed as indicated by the panel sequence. Such abnormalities are a result of the nanotube interacting with the dynamic cellular elements involved in the mitotic spindle formation, namely microtubule and DNA. (Reprinted with permission from Ref . Copyright 2012 American Chemical Society)
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In vivo and in vitro exposure to carbon nanotubes (CNTs) led to cytotoxic and genotoxic effects. A summary of the toxicological mechanisms induced by single‐walled (SWCNTs) and multiwalled carbon nanotubes (MWCNTs) and the associated references are shown.
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(a) Schematic diagram of a localized tumor treatment with carbon nanotubes (CNTs). Upon cellular uptake, CNTs serve as scaffold for biohybrid assembly. Specifically, free tubulin present in the cellular environment polymerizes on the nanotube structure to form a modified microtubule. (b) Biohybrids incorporation into the cellular division apparatus leads to abnormal cell division. Molecular motors normally involved in the mitotic spindle formation are engaging in a tug‐of‐war or dissociate from the biohybrids. Motors mis‐coordination leads to programmed cancer cell death.
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Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials

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