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Long-term biocompatibility of fluorescent diamonds-(NV)-Z~800 nm in rats: survival, morbidity, histopathology, and particle distribution and excretion studies (part IV)

Authors Barone FC, Marcinkiewicz C, Li J, Feng Y, Sternberg M, Lelkes PI, Rosenbaum-Halevi D, Gerstenhaber JA, Feuerstein GZ

Received 28 September 2018

Accepted for publication 15 January 2019

Published 14 February 2019 Volume 2019:14 Pages 1163—1175

DOI https://doi.org/10.2147/IJN.S189048

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Alexander Kharlamov

Peer reviewer comments 2

Editor who approved publication: Dr Thomas J Webster


Frank C Barone,1 Cezary Marcinkiewicz,2,3 Jie Li,1 Yi Feng,4 Mark Sternberg,2 Peter I Lelkes,3 David Rosenbaum-Halevi,5 Jonathan A Gerstenhaber,3 Giora Z Feuerstein2

1SUNY Downstate Medical Center, Department of Neurology, Brooklyn, NY, USA; 2Debina Diagnostic Inc., Newtown Square, PA, USA; 3Department of Bioengineering, Temple University, College of Engineering, Philadelphia, PA, USA; 4WuXi AppTec (Suzhou) Co., Ltd., China; 5Texas University Health Center, TMC, Houston, TX, USA

Background: Thromboembolic events are a major cause of heart attacks and strokes. However, diagnosis of the location of high risk vascular clots is hampered by lack of proper technologies for their detection .We recently reported on bio-engineered fluorescent diamond-(NV)-Z~800nm (FNDP-(NV)) conjugated with bitistatin (Bit) and proven its ability to identify iatrogenic blood clots in the rat carotid artery in vivo by Near Infra-Red (NIR) monitored by In Vivo Imaging System (IVIS).
Purpose: The objective of the present research was to assess the in vivo biocompatibility of FNDP-(NV)-Z~800nm infused intravenously to rats. Multiple biological variables were assessed along this 12 week study commissioned in anticipation of regulatory requirements for a long-term safety assessment.
Methods: Rats were infused under anesthesia with aforementioned dose of the FNDP-(NV), while equal number of animals served as control (vehicle treated). Over the 12 week observation period rats were tested for thriving, motor, sensory and cognitive functions. At the termination of study, blood samples were obtained under anesthesia for comprehensive hematology and biochemical assays. Furthermore, 6 whole organs (liver, spleen, brain, heart, lung and kidney) were collected and examined ex vivo for FNDP-NV) via NIR monitored by IVIS and histochemical inspection.
Results: All animals survived, thrived (no change in body and organ growth). Neuro-behavioral functions remain intact. Hematology and biochemistry (including liver and kidney functions) were normal. Preferential FNDP-(NV) distribution identified the liver as the main long- term repository. Certified pathology reports indicated no outstanding of finding in all organs.
Conclusion: The present study suggests outstanding biocompatibility of FNDP-(NV)-Z~800nm after long-term exposure in the rat.

Keywords: nanocarbon particles, biocompatibility, liver toxicology, ex vivo IR organ imaging

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