Microtubule cytoskeleton-disrupting activity of MWCNTs: applications in cancer treatment

Hevia, Lorena García; Fanarraga, Mónica L.

doi:10.1186/s12951-020-00742-y

Cited by 20 publications

(9 citation statements)

References 80 publications

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“…Notably, these two materials show larger particle sizes in the cells (Figure S5), as TiO 2 NCs seem to locally cluster inside cells (Figures S6-S7 with additional high-resolution and correlative light and ion microscopy data). MWCNTs seem to anchor and entangle with microtubule structure that could potentially disrupt cell flexural rigidity 34 and eventually lead to cell apoptosis 35 . Further differences between nanoparticles are discussed in the supplementary comment #1 in Supporting information Appendix section.…”

Section: Resultsmentioning

confidence: 99%

Binucleated cell formation and oncogene expression after particulate matter exposure is preceded by microtubule disruption, dysregulated cell cycle, prolonged mitosis, and septin binding

Podlipec,

Sebastijanovič,

Cassidy

et al. 2024

Preprint

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Several biopersistent high aspect ratio nanomaterials show pronounced pathogenic effects, from chronic lung inflammation and fibrosis to cancer. For example, asbestos fibers are classified as carcinogens, whereas the carcinogenicity of highly inflammatory multi-wall carbon nanotubes (MWCNTs), and TiO2 nanomaterials is still being evaluated. The exact early mechanisms of their pathogenicity towards inflammation and cancer remains uncertain, but it is likely not due to genotoxic or mutagenic activity. A proposed early mode of action that might lead to the formation of cancerous cells for asbestos fibers is the formation of binucleated and multinucleated cells, resulting in genetic instability. Here, we show that two high aspect ratio nanomaterials, MWCNTs and TiO2 nanotubes, which both induce chronic lung inflammation, induce very different cancer-related changes in vitro. TiO2 nanotubes, but not low aspect-ratio nanocubes of the same crystalline structure, disrupt microtubule organization and prolong mitosis, as well as deform nuclear shape, induce the formation of binucleated cells, and downregulate the tumour suppressor protein p53, whereas only the MWCNTs activate the stimulator of the interferon genes (STING) pathway, a hallmark of lung cancer. The observed differences in cellular responses to different high aspect ratio materials imply the need for assessing each nanomaterial individually with a broad range of tests rather than relying solely on a single marker or pathway, or even morphological or bulk chemical properties to infer possible carcinogenic properties.

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Section: Resultsmentioning

confidence: 99%

Binucleated cell formation and oncogene expression after particulate matter exposure is preceded by microtubule disruption, dysregulated cell cycle, prolonged mitosis, and septin binding

Podlipec,

Sebastijanovič,

Cassidy

et al. 2024

Preprint

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“…This synergism can promote the antitumor effects of standard drugs and inhibit resistance among cancer cells. 52 …”

Section: Rationale For the Cytotoxic Effects Of Cnts On Cancer Cellsmentioning

confidence: 99%

Carbon Nanotubes as Carriers in Drug Delivery for Non-Small Cell Lung Cancer, Mechanistic Analysis of Their Carcinogenic Potential, Safety Profiling and Identification of Biomarkers

Pu¹,

Wei²,

Sun³

et al. 2022

IJN

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Non-small cell lung cancer (NSCLC) is a global burden leading to millions of deaths worldwide every year. Nanomedicine refers to the use of materials at the nanoscale for drug delivery and subsequent therapeutic approaches in cancer. Carbon nanotubes (CNTs) are widely used as nanocarriers for therapeutic molecules such as plasmids, siRNAs, antisense agents, aptamers and molecules related to the immunotherapy for several cancers. They are usually functionalized and loaded with standard drug molecules to improve their therapeutic efficiency. Functionalization and drug loading possibly decrease the genotoxic and carcinogenic potential of CNTs. In addition, the targeted cytotoxic properties of the drug improve and undesired toxicity decreases after drug loading and/or conjugation with proteins, including antibodies. For intended drug delivery, a lysosomal pH of 5.5 is more suitable and effective for the slow and extended release of cytotoxic drugs than a physiological of pH 7.4. Remarkably, CNTs possess intrinsic antitumor properties and are usually internalized by endocytosis. After being internalized, several mechanisms are involved in the therapeutic and carcinogenic effects of CNTs. They are generally safe for therapy, and their toxicity profile remains dependent on their physicochemical properties. Moreover, the dose, route, duration of exposure, surface properties and degradative potential determine the toxicity outcomes of CNTs locally or systemically. In summary, the use of CNTs in drug delivery and NSCLC therapy, as well as their genotoxic and carcinogenic potential and the possible mechanisms, has been discussed in this review. The therapeutic index is generally high for NSCLC cells treated with drug-loaded CNTs; therefore, they are effective carriers in implementing targeted therapy for NSCLC.

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“…Carbon nanotubes (CNTs) are a close synthetic equivalent to biological microtubules. In specific, multiwalled CNTs exhibit similarities in both size and shape to microtubules and have been shown to possess microtubule biomimetic properties through the modification of microtubule assembly and stabilization within cells [3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Chemical-induced changes in the optical properties of aromatic amino acid lattices in protein polymers

Craddock,

Hedrick,

De Abreu

2024

Quantum Effects and Measurement Techniques in Biology and Biophotonics

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Microtubules are self-assembling biological helical nanotubes made of the protein tubulin that are essential for cell motility, cell architecture, cell division, molecular signaling, and intracellular trafficking. It has been hypothesized that this hollow molecular nanostructure may support optical transitions in photoexcited tryptophan, tyrosine, or phenylalanine amino acid lattices to function as a light-harvester in similar fashion as photosynthetic units; this ability coupled with its shape is analogous to a quantum wire. In support of this, recent experimental work demonstrates that electronic energy can diffuse across microtubules in a manner that cannot be explained by conventional Förster theory making them effective light harvesters. Here we present theoretical work of energy transfer between amino acids in tubulin via dipole excitations in the presence and absence of a chemical perturbation. Results demonstrate the potential for chemical manipulation of the optical properties of aromatic amino acid lattices in microtubule protein structures.

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Microtubule cytoskeleton-disrupting activity of MWCNTs: applications in cancer treatment

Cited by 20 publications

References 80 publications

Binucleated cell formation and oncogene expression after particulate matter exposure is preceded by microtubule disruption, dysregulated cell cycle, prolonged mitosis, and septin binding

Binucleated cell formation and oncogene expression after particulate matter exposure is preceded by microtubule disruption, dysregulated cell cycle, prolonged mitosis, and septin binding

Carbon Nanotubes as Carriers in Drug Delivery for Non-Small Cell Lung Cancer, Mechanistic Analysis of Their Carcinogenic Potential, Safety Profiling and Identification of Biomarkers

Chemical-induced changes in the optical properties of aromatic amino acid lattices in protein polymers

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