Gd-metallofullerenol nanomaterial as non-toxic breast cancer stem cell-specific inhibitor

Liu, Ying; Chen, Chunying; Qian, Pengxu; Lu, Xuefei; Sun, Baoyun; Zhang, Xiao; Wang, Liming; Gao, Xingfa; Liang, Han; Chen, Zhiyun; Tang, Jinglong; Zhang, Weijie; Dong, Jinquan; Bai, Ru; Lobie, Peter E.; Wu, Qingfa; Liu, Suling; Zhang, Huafeng; Zhao, Feng; Wicha, Max S.; Zhu, Tao; Zhao, Yuliang

doi:10.1038/ncomms6988

Cited by 171 publications

(117 citation statements)

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“…This therefore provides a perfect example of a specific nanoscale interaction between a synthetic nanoparticle and a biological receptor (protein) that can be harnessed for therapeutic gain. More recently, Liu et al (59) reported that Gd@C 82 (OH) 22 are essentially nontoxic to normal mammary epithelial cells, while these nanoparticles possess intrinsic inhibitory activity against triple-negative breast cancer cells. Moreover, the authors provided evidence that the nanoparticles specially inhibited so-called breast cancer stem cells, resulting in the abrogation of tumor initiation and metastasis (59).…”

Section: The Other Side Of the Coin: Nanomedicinementioning

confidence: 99%

“…More recently, Liu et al (59) reported that Gd@C 82 (OH) 22 are essentially nontoxic to normal mammary epithelial cells, while these nanoparticles possess intrinsic inhibitory activity against triple-negative breast cancer cells. Moreover, the authors provided evidence that the nanoparticles specially inhibited so-called breast cancer stem cells, resulting in the abrogation of tumor initiation and metastasis (59). They found that under hypoxic conditions in the tumor microenvironment, crucial surface modifications of the Gd-metallofullerenol occurred, which promoted tumor uptake, enhancing the elimination of cancer stem cells.…”

Section: The Other Side Of the Coin: Nanomedicinementioning

confidence: 99%

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Keeping it small: towards a molecular definition of nanotoxicology

Gallud

Fadeel

2015

European Journal of Nanomedicine

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Abstract:In this essay, we offer the opinion that engineered nanomaterials are, by definition, materials that can interact with biological systems at the nanoscale, and that this very fact underlies both the promise and the peril of this multifaceted class of materials. Furthermore, nanomaterials are cloaked in host-derived proteins, lipids, or other biomolecules as they enter into a living organism and this so-called bio-corona may impact on subsequent interactions with biological structures. We will explore some examples of nanoscale effects of engineered nanomaterials, and discuss how such interactions may underpin toxicity, and, conversely, how nanoscale interactions may be harnessed for clinical applications, including the use of nanoparticles as drugs per se.Keywords: biological mimicry; cellular nanomachineries; engineered nanomaterials; molecular dynamics simulations; nanomedicine; nanotopographies; nanotoxicology. Life is a nanoscale phenomenonIn their seminal paper published one decade ago, Donaldson et al. (1) proposed that a new subcategory of toxicology -namely nanotoxicology -be defined to specifically address "the special problems likely to be caused by nanoparticles", and the authors suggested that nanotoxicology be considered "a new frontier in particle toxicology". However, one may argue, instead, that nanotoxicology represents a departure from the traditional toxicology of fine and ultrafine particles and fibers. In fact, nanotoxicology may be understood in light of "the interference of engineered nanomaterials with the functions of cellular and extracellular nanomachineries" (2). This view places emphasis on the fact that life (biology) is "a nanoscale phenomenon" (3). Indeed, living organisms are host to a range of dedicated intra-and extracellular nanoscale machines (4) and this, therefore, suggests that specific, size-dependent toxicities may ensue as a result of exposure to engineered nanomaterials. This does not, however, mean that all nanomaterials are inherently toxic (5), or that a nanospecific effect is necessarily detrimental to the host; in fact, the controlled manipulation of biological systems at the nanoscale may very well open up for novel therapeutic approaches. In this essay, we will explore both sides of the coin. The right size in nanotoxicologyIn his review on "the 'right' size in nanobiotechnology", Whitesides argued that "small" -both nano and micromust be a part of the future of biotechnology; which size is most important depends on what question one is asking (6). Surprisingly, in the field of nanotoxicology, the question of size, and more specifically, how one should define a nanomaterial (indeed, whether or not one should define nanomaterials in the first place) remains a matter of debate. Hence, while some have argued that we should not define nanomaterials, or to be more precise, that a 'one-size-fitsall' definition of nanomaterials will fail to capture what is important for addressing risk (7), others have stated that a definition of nanomaterials for regulatory ...

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Section: The Other Side Of the Coin: Nanomedicinementioning

confidence: 99%

Section: The Other Side Of the Coin: Nanomedicinementioning

confidence: 99%

Keeping it small: towards a molecular definition of nanotoxicology

Gallud

Fadeel

2015

European Journal of Nanomedicine

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“…110,111 Liu et al recognised that, while sharing the same number of hydroxyl groups, Gd@C 82 (OH) 22 outperformed C 60 (OH) 22 in the inhibition of breast cancer metastasis. 112 This is a good demonstration of the effect of the incarcerated species in EMFs on their reactivity, structure and subsequent function. Chen et al found the antineoplastic activity of Gd@C 82 (OH) 22 was considerably greater than that of commonly used cis-platin, thus adding weight to the claim for fullerenes to be used as chemotherapeutic agents.…”

Section: Chemotherapymentioning

confidence: 99%

Water-soluble fullerenes for medical applications

Rašović

2017

Materials Science and Technology

118

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Research on fullerenes occupies a unique position in the scientific arena. Synthesis and characterisation of this nanomaterial blur the line between materials science and chemistry; careful tuning of the processing methods gives birth to a whole family of molecules and their functionalised derivatives, whose unusual properties at this nanoscopic scale can be exploited in cutting-edge technological applications. This review focuses on the functionalisation of fullerenes for use in medical applications. The first half gives an introduction to the fullerenes themselves and how their fundamental properties lead to a very rich chemistry, enabling both exohedral (external) and endohedral (internal) functionalisations of the cage. Emphasis is placed on the need for safe and reproducible synthesis routes if fullerenes are ever going to make it to the pharmaceutical market. In line with this, a selection of exohedral functionalisation protocols receives particular attention. Coverage of endohedral fullerene synthesis routes is limited to the endohedral metallofullerenes. In the second half, myriad applications of fullerenes in biomedical contexts are introduced and certain synthesis routes are critically evaluated. Discussion of the need to water solubilise the hydrophobic fullerene cages precedes an overview of fullerene-based diagnostic and therapeutic technologies. A final moment is spent on toxicity studies of fullerenes. The concluding remarks emphasise the positive effects of incorporating fullerenes into biomedical technologies, while looking at how these are perceived by the general public. A case is made for fullerenes being the optimal choice as standard bearers in the advance of nanomaterials into the medical field. This is the winning review of the 2016 Materials Literature Review Prize of the Institute of Materials, Minerals and Mining, run by the Editorial Board of MST. Sponsorship of the prize by TWI Ltd is gratefully acknowledged.

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“…For example, graphene oxide can selectively induce CSC differentiation by inhibiting multiple key pathways for CSC self-renewal including WNT, Notch and STAT-signaling. Since graphene oxide is non-toxic, this therapeutic strategy is promising for CSC eradication [106]. The metallofullerenol nanomaterial, Gd@C82(OH)22, can block epithelialto-mesenchymal transition with resultant efficient elimination of breast CSCs, potentially through a bi-potent inhibition of HIF-1α and TGF-β activities [107].…”

Section: Targeting Lscs By Nanomedicinementioning

confidence: 99%