Carbon nanotubes exhibit fibrillar pharmacology in primates

Alidori, Simone; Thorek, Daniel L.J.; Beattie, Bradley J.; Ulmert, David; Almeida, Bryan Aristega; Monette, Sébastien; Scheinberg, David A.; McDevitt, Michael R.

doi:10.1371/journal.pone.0183902

Cited by 23 publications

(17 citation statements)

References 27 publications

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“…Alternatively, the nanosensors may be embedded directly in a hydrogel matrix, as has been investigated with carbon nanotubes in vivo, finding no local inflammation ( 27 ). Further, although we expect no exposure of the nanosensor complex when immobilized in the implant device, well-dispersed, purified SWCNTs such as those used here do not exhibit any immunogenic or toxic effects ( 36 , 53 ).…”

Section: Discussionmentioning

confidence: 91%

Noninvasive ovarian cancer biomarker detection via an optical nanosensor implant

et al. 2018

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Section: Discussionmentioning

confidence: 91%

Noninvasive ovarian cancer biomarker detection via an optical nanosensor implant

et al. 2018

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“…Fibrillar macromolecules that are rigid and have high-aspect ratios exhibit unique pharmacological properties in vivo compared to high molecular weight globular molecules 11 , 12 . Our lab has been investigating functionalized carbon nanotubes (fCNT) as synthetic molecular platforms for gene and drug delivery 13 – 20 . Several physicochemical properties are common to CNT and CNC including high surface area, rigid fibrillar shape, high aspect ratio and a minimal aqueous solubility of the unfunctionalized starting materials.…”

Section: Introductionmentioning

confidence: 99%

“…Surface modification of CNT with multiple copies of primary amines provided a means to greatly improve water-solubility and biocompatibility as well as an expedient means to engineer a drug excipient for loading and transport of pharmacologically active cargo. The exceptional pharmacokinetic behavior of functionalized CNT in rodents and nonhuman primates is best described by rapid blood clearance, cell specific-accumulation in kidney and liver and intact renal elimination in the urine 13 – 15 , 18 .…”

Section: Introductionmentioning

confidence: 99%

Fibrillar pharmacology of functionalized nanocellulose

Wong

Alidori

Mello

et al. 2021

Sci Rep

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Cellulose nanocrystals (CNC) are linear organic nanomaterials derived from an abundant naturally occurring biopolymer resource. Strategic modification of the primary and secondary hydroxyl groups on the CNC introduces amine and iodine group substitution, respectively. The amine groups (0.285 mmol of amine per gram of functionalized CNC (fCNC)) are further reacted with radiometal loaded-chelates or fluorescent dyes as tracers to evaluate the pharmacokinetic profile of the fCNC in vivo. In this way, these nanoscale macromolecules can be covalently functionalized and yield water-soluble and biocompatible fibrillar nanoplatforms for gene, drug and radionuclide delivery in vivo. Transmission electron microscopy of fCNC reveals a length of 162.4 ± 16.3 nm, diameter of 11.2 ± 1.52 nm and aspect ratio of 16.4 ± 1.94 per particle (mean ± SEM) and is confirmed using atomic force microscopy. Size exclusion chromatography of macromolecular fCNC describes a fibrillar molecular behavior as evidenced by retention times typical of late eluting small molecules and functionalized carbon nanotubes. In vivo, greater than 50% of intravenously injected radiolabeled fCNC is excreted in the urine within 1 h post administration and is consistent with the pharmacological profile observed for other rigid, high aspect ratio macromolecules. Tissue distribution of fCNC shows accumulation in kidneys, liver, and spleen (14.6 ± 6.0; 6.1 ± 2.6; and 7.7 ± 1.4% of the injected activity per gram of tissue, respectively) at 72 h post-administration. Confocal fluorescence microscopy reveals cell-specific accumulation in these target tissue sinks. In summary, our findings suggest that functionalized nanocellulose can be used as a potential drug delivery platform for the kidneys.

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“…In this study, we found no safety issues with MNPs, which comports with our prior work in healthy mice 17 . However, the nanotube-based drug carrier also demonstrated safety in non-human primates 37,38 . We expect similar pre-clinical pharmacokinetic studies to further the possibility of MNP clinical translation.…”

Section: Discussionmentioning

confidence: 99%

Edaravone-Loaded Mesoscale Nanoparticles Treat Cisplatin-Induced Acute Kidney Injury

Williams

Shah

Mercer

et al. 2020

Preprint

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Cisplatin-induced acute kidney injury (CI-AKI) is a significant co-morbidity of chemotherapeutic regimens. While this condition is associated with substantially lower survival and increased economic burden, there is no pharmacological agent to effectively treat CI-AKI. The disease is hallmarked by acute tubular necrosis of the proximal tubular epithelial cells primarily due to increased oxidative stress. In our prior work, we developed a highly-selective kidneytargeted mesoscale nanoparticle (MNP) that accumulates primarily in the renal proximal tubular epithelial cells while exhibiting no toxicity. Here, we found that MNPs exhibit renal-selective targeting in multiple mouse models of tumor growth with virtually no tumor accumulation. We then evaluated the therapeutic efficacy of MNPs loaded with the reactive oxygen species scavenger edaravone in a mouse model of CI-AKI. We found a marked and significant therapeutic effect with this approach as compared to free drug or empty control MNPs, including improved renal function, histology, and diminution of oxidative stress. These results indicated that renal-selective MNP edaravone delivery holds substantial potential in the treatment of acute kidney injury among patients undergoing cisplatin-based chemotherapy. Acute kidney injury (AKI) is a common clinical condition associated with significant morbidity and mortality regardless of etiology or setting. AKI affects millions of individual patients and has a large socioeconomic impact, including longer hospital stay and higher costs. In the US alone, it is estimated that the annual costs related to AKI are up to $24 billion 1 . The incidence of AKI is increasing at a rapid pace 2,3 , which is attributable to several factors including shifts in demographics, severity of underlying diseases, and expansion of invasive and complex medical procedures 4,5 . AKI can result from a variety of insults including volume depletion, septicemia, hypotension, and commonly used drugs including antibiotics and chemotherapeutic agents.Cisplatin is a widely used chemotherapy in the treatment of a variety of cancers including ovarian, head and neck, bladder, testicular, and lung, among others 6,7 . A significant side effect of cisplatin therapy is the occurrence of AKI in approximately 33% of patients 8,9 . Indeed, it has been reported that about 20% of all AKI incidences are caused by cisplatin 7,10 . The development of AKI in these patients can result in the interruption of chemotherapy or a change to less effective chemotherapies 8,9 . There is therefore a critical need to develop novel strategies to prevent or treat AKI induced by cisplatin. This would also have a direct impact on the oncologic outcomes of these patients whose treatment otherwise cannot be completed, or other less-effective chemotherapeutic agents must be used 11 .There has been significant overall progress in our understanding of the epidemiology, pathophysiology and outcomes of AKI. Despite such substantial advances, almost no meaningful progress has been made in the ...

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Carbon nanotubes exhibit fibrillar pharmacology in primates

Cited by 23 publications

References 27 publications

Noninvasive ovarian cancer biomarker detection via an optical nanosensor implant

Noninvasive ovarian cancer biomarker detection via an optical nanosensor implant

Fibrillar pharmacology of functionalized nanocellulose

Edaravone-Loaded Mesoscale Nanoparticles Treat Cisplatin-Induced Acute Kidney Injury

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