Physical Factors Affecting Kinesin-Based Transport of Synthetic Nanoparticle Cargo

Bachand, Marlene; Trent, Amanda; Bunker, Bruce C.; Bachand, George D.

doi:10.1166/jnn.2005.112

Cited by 86 publications

(91 citation statements)

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“…Although inhibition of the cellular motors has not been demonstrated with carbon nanotubes, spherical nanoparticles of 40 nanometers or less have been shown to inhibit the mitotic spindle motor kinesin which is essential for normal cell division [55]. Furthermore, carbon nanotubes form hybrids with microtubules that were transported by the cellular motors [56].…”

Section: Discussionmentioning

confidence: 99%

Single-walled carbon nanotube-induced mitotic disruption

Sargent

Hubbs

Young

et al. 2012

Mutation Research/Genetic Toxicology and Environmental Mutagene

146

123

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Carbon nanotubes were among the earliest products of nanotechnology and have many potential applications in medicine, electronics, and manufacturing. The low density, small size, and biological persistence of carbon nanotubes create challenges for exposure control and monitoring and make respiratory exposures to workers likely. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to 24, 48 and 96 μg/cm 2 single-walled carbon nanotubes (SWCNT). To investigate mitotic spindle aberrations at concentrations anticipated in exposed workers, primary and immortalized human airway epithelial cells were exposed to SWCNT for 24-72 h at doses equivalent to 20 weeks of exposure at the Permissible Exposure Limit for particulates not otherwise regulated. We have now demonstrated fragmented centrosomes, disrupted mitotic spindles and aneuploid chromosome number at those doses. The data further demonstrated multipolar mitotic spindles comprised 95% of the disrupted mitoses. The increased multipolar mitotic spindles were associated with an increased number of cells in the G2 phase of mitosis, indicating a mitotic checkpoint response. Nanotubes were observed in association with mitotic spindle microtubules, the centrosomes and condensed chromatin in cells exposed to 0.024, 0.24, 2.4 and 24 μg/cm 2 SWCNT. Three- Conflict of interest statementThe authors declare that there are no conflicts of interest. Appendix A. Supplementary dataSupplementary data associated with this article can be found, in the online version, at doi:10.1016/j.mrgentox.2011.11.017. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript dimensional reconstructions showed carbon nanotubes within the centrosome structure. The lower doses did not cause cytotoxicity or reduction in colony formation after 24 h; however, after three days, significant cytotoxicity was observed in the SWCNT-exposed cells. Colony formation assays showed an increased proliferation seven days after exposure. Our results show significant disruption of the mitotic spindle by SWCNT at occupationally relevant doses. The increased proliferation that was observed in carbon nanotube-exposed cells indicates a greater potential to pass the genetic damage to daughter cells. Disruption of the centrosome is common in many solid tumors including lung cancer. The resulting aneuploidy is an early event in the progression of many cancers, suggesting that it may play a role in both tumorigenesis and tumor progression. These results suggest caution should be used in the handling and processing of carbon nanotubes.

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Section: Discussionmentioning

confidence: 99%

Single-walled carbon nanotube-induced mitotic disruption

Sargent

Hubbs

Young

et al. 2012

Mutation Research/Genetic Toxicology and Environmental Mutagene

146

123

View full text Add to dashboard Cite

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“…Cationic lipids dissociate from DNA through lipid mixing and exchange with host cell lipids at the cytoplasm entry step, while DNA complexes formed with cationic polymers, such as PEI, remain stable after endosome escape. An interesting concept has been reported recently, under which the intracellular trafficking of DNA-loaded nanoparticles is coupled with microtubule-directed transport mechanism (14). The polymer-DNA complexes disintegrate later in nucleus (15).…”

Section: Extra-and Intracellular Barriers For Gene Deliverymentioning

confidence: 99%

Nonviral Gene Delivery: Principle, Limitations, and Recent Progress

Al‐Dosari

Gao

2009

AAPS J

592

438

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Abstract. Gene therapy is becoming a promising therapeutic modality for the treatment of genetic and acquired disorders. Nonviral approaches as alternative gene transfer vehicles to the popular viral vectors have received significant attention because of their favorable properties, including lack of immunogenicity, low toxicity, and potential for tissue specificity. Such approaches have been tested in preclinical studies and human clinical trials over the last decade. Although therapeutic benefit has been demonstrated in animal models, gene delivery efficiency of the nonviral approaches remains to be a key obstacle for clinical applications. This review focuses on existing and emerging concepts of chemical and physical methods for delivery of therapeutic nucleic acid molecules in vivo. The emphasis is placed on discussion about problems associated with current nonviral methods and recent efforts toward refinement of nonviral approaches.

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“…The long-term application of this work centers on the energy-driven assembly of photoactive materials with a range of materials science-, nanoelectronics-, and nanophotonics-based applications. There has been considerable interest in using biological molecules as scaffolds for synthesizing and assembling nanoscale materials [26][27][28][29][30][31][32][33][34]. To date, the majority of work has focused on using biomolecules as a static scaffold for assembling composite materials.…”

Section: Figure 10mentioning

confidence: 99%

Assembling semiconductor nanocomposites using DNA replication technologies.

Heimer¹,

Crown²,

Bachand³

2005

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Deoxyribonucleic acid (DNA) molecules represent Nature's genetic database, encoding the information necessary for all cellular processes. From a materials engineering perspective, DNA represents a nanoscale scaffold with highly refined structure, stability across a wide range of environmental conditions, and the ability to interact with a range of biomolecules. The ability to mass-manufacture functionalized DNA strands with Ångstrom-level resolution through DNA replication technology, however, has not been explored. The long-term goal of the work presented in this report is focused on exploiting DNA and in vitro DNA replication processes to mass-manufacture nanocomposite materials. The specific objectives of this project were to: (1) develop methods for replicating DNA strands that incorporate nucleotides with "chemical handles," and (2) demonstrate attachment of nanocrystal quantum dots (nQDs) to functionalized DNA strands. Polymerase chain reaction (PCR) and primer extension methodologies were used to successfully synthesize amine-, thiol-, and biotin-functionalized DNA molecules. Significant variability in the efficiency of modified nucleotide incorporation was observed, and attributed to the intrinsic properties of the modified nucleotides. Noncovalent attachment of streptavidin-coated nQDs to biotin-modified DNA synthesized using the primer extension method was observed by epifluorescence microscopy. Data regarding covalent attachment of nQDs to amine-and thiol-functionalized DNA was generally inconclusive; alternative characterization tools are necessary to fully evaluate these attachment methods. Full realization of this technology may facilitate new approaches to manufacturing materials at the nanoscale. In addition, composite nQD-DNA materials may serve as novel recognition elements in sensor devices, or be used as 3 diagnostic tools for forensic analyses. This report summarizes the results obtained over the course of this 1-year project.

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Physical Factors Affecting Kinesin-Based Transport of Synthetic Nanoparticle Cargo

Cited by 86 publications

References 0 publications

Single-walled carbon nanotube-induced mitotic disruption

Single-walled carbon nanotube-induced mitotic disruption

Nonviral Gene Delivery: Principle, Limitations, and Recent Progress

Assembling semiconductor nanocomposites using DNA replication technologies.

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