Targeting Breast Cancer with Sugar-Coated Carbon Nanotubes

Fahrenholtz, Cale D.; Hadimani, Mallinath B.; King, S. Bruce; Torti, Suzy V.; Singh, Ravi

doi:10.2217/nnm.15.90

Cited by 36 publications

(38 citation statements)

References 68 publications

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“…As we previously reported, these MWCNTs were generally 100–200 nm in length and retained diameters of 8–15 nm 35 . MWCNTs were then dispersed by sonication in water (uncoated) or an aqueous solution of 2% weight/volume (w/vol) distearylphosphatidylethanolamine-polyethylene glycol 5000 (DSPE-PEG).…”

Section: Resultssupporting

confidence: 71%

“…However, when cells were grown as three dimensional spheroids rather than as monolayers, MWCNTs appeared to have no effect on growth and thus their toxicity may be highly context dependent. It is notable that despite the increased toxicity we find in vitro for DSPE-PEG coated MWCNTs relative to uncoated or Pluronic F127 coated MWCNTs, both acid-oxidation and DSPE-PEG-coating have been shown to mitigate acute CNT toxicity in vivo 19, 35 . A growing body of evidence suggests the existence of multiple in vivo biodegradation mechanisms for CNTs 56, 57 , and that CNTs can safely be used in the brain 20, 58–60 .…”

Section: Discussionmentioning

confidence: 77%

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Photothermal Therapy of Glioblastoma Multiforme Using Multiwalled Carbon Nanotubes Optimized for Diffusion in Extracellular Space

Eldridge

Bernish

Fahrenholtz

et al. 2016

ACS Biomater. Sci. Eng.

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Glioblastoma multiforme (GBM) is the most common and most lethal primary brain tumor with a 5 year overall survival rate of approximately 5%. Currently, no therapy is curative and all have significant side effects. Focal thermal ablative therapies are being investigated as a new therapeutic approach. Such therapies can be enhanced using nanotechnology. Carbon nanotube mediated thermal therapy (CNMTT) uses lasers that emit near infrared radiation to excite carbon nanotubes (CNTs) localized to the tumor to generate heat needed for thermal ablation. Clinical translation of CNMTT for GBM will require development of effective strategies to deliver CNTs to tumors, clear structure-activity and structure-toxicity evaluation, and an understanding of the effects of inherent and acquired thermotolerance on the efficacy of treatment. In our studies, we show that a dense coating of phospholipid-poly(ethylene glycol) on multiwalled CNTs (MWCNTS) allows for better diffusion through brain phantoms, while maintaining the ability to achieve ablative temperatures after laser exposure. Phospholipid-poly(ethylene glycol) coated MWCNTs do not induce a heat shock response (HSR) in GBM cell lines. Activation of the HSR in GBM cells via exposure to sub-ablative temperatures or short term treatment with an inhibitor of heat shock protein 90 (17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG)), induces a protective heat shock response that results in thermotolerance and protects against CNMTT. Finally, we evaluate the potential for CNMTT to treat GBM multicellular spheroids. These data provide pre-clinical insight into key parameters needed for translation of CNMTT including nanoparticle delivery, cytotoxicity, and efficacy for treatment of thermotolerant GBM.

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Section: Resultssupporting

confidence: 71%

Section: Discussionmentioning

confidence: 77%

Photothermal Therapy of Glioblastoma Multiforme Using Multiwalled Carbon Nanotubes Optimized for Diffusion in Extracellular Space

Eldridge

Bernish

Fahrenholtz

et al. 2016

ACS Biomater. Sci. Eng.

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“…We previously showed that conjugation of glucosamine to the MWCNT surface does not affect the cell binding affinity or uptake of the MWCNTs(Fahrenholtz et al, 2015). To evaluate whether the observed increased toxicity of coated MWCNTs compared to uncoated MWCNTs was due to differences in cellular uptake, HBMECs were plated on plastic in monolayer and were exposed to cut uncoated or cut coated 3 H-MWCNT.…”

Section: Resultsmentioning

confidence: 99%

“…Acid treatment and purification of the MWCNTs was performed as we previously described(Fahrenholtz et al, 2015). DSPE-PEG 5000 (Nanocs, Inc.) was dissolved at a concentration of 2% weight to volume in deionized water.…”

Section: Methodsmentioning

confidence: 99%

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Evaluation of multiwalled carbon nanotube cytotoxicity in cultures of human brain microvascular endothelial cells grown on plastic or basement membrane

Eldridge

Xing

Fahrenholtz

et al. 2017

Toxicology in Vitro

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There is a growing interest in the use of multiwalled carbon nanotubes (MWCNTs) to treat diseases of the brain. Little is known about the effects of MWCNTs on human brain microvascular endothelial cells (HBMECs), which make up the blood vessels in the brain. In our studies, we evaluate the cytotoxicity of MWCNTs and acid oxidized MWNCTs, with or without a phospholipid-polyethylene glycol coating. We determined the cytotoxic effects of MWCNTs on both tissue-mimicking cultures of HBMECs grown on basement membrane and on monolayer cultures of HBMECs grown on plastic. We also evaluated the effects of MWCNT exposure on the capacity of HBMECs to form rings after plating on basement membrane, a commonly used assay to evaluate angiogenesis. We show that tissue-mimicking cultures of HBMECs are less sensitive to all types of MWCNTs than monolayer cultures of HBMECs. Furthermore, we found that MWCNTs have little impact on the capacity of HBMECs to form rings. Our results indicate that relative cytotoxicity of MWCNTs is significantly affected by the type of cell culture model used for testing, and supports further research into the use of tissue-mimicking endothelial cell culture models to help bridge the gap between in vitro and in vivo toxicology.

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A Safe‐by‐Design Strategy towards Safer Nanomaterials in Nanomedicines

et al. 2019

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The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201805391.The marriage of nanotechnology and medicine offers new opportunities to fight against human diseases. Benefiting from their unique optical, thermal, magnetic, or redox properties, a wide range of nanomaterials have shown potential in applications such as diagnosis, drug delivery, or tissue repair and regeneration. Despite the considerable success achieved over the past decades, the newly emerging nanomedicines still suffer from an incomplete understanding of their safety risks, and of the relationships between their physicochemical characteristics and safety profiles. Herein, the most important categories of nanomaterials with clinical potential and their toxicological mechanisms are summarized, and then, based on this available information, an overview of the principles in developing safe-by-design nanomaterials for medical applications and of the recent progress in this field is provided. These principles may serve as a starting point to guide the development of more effective safe-by-design strategies and to help identify the major knowledge and skill gaps.

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Targeting Breast Cancer with Sugar-Coated Carbon Nanotubes

Cited by 36 publications

References 68 publications

Photothermal Therapy of Glioblastoma Multiforme Using Multiwalled Carbon Nanotubes Optimized for Diffusion in Extracellular Space

Photothermal Therapy of Glioblastoma Multiforme Using Multiwalled Carbon Nanotubes Optimized for Diffusion in Extracellular Space

Evaluation of multiwalled carbon nanotube cytotoxicity in cultures of human brain microvascular endothelial cells grown on plastic or basement membrane

A Safe‐by‐Design Strategy towards Safer Nanomaterials in Nanomedicines

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