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Barone FC , Marcinkiewicz C , Li J , Feng Y , Sternberg M , Lelkes PI , Rosenbaum-Halevi D , Gerstenhaber JA , Feuerstein GZ
Long-term biocompatibility of fluorescent diamonds-(NV)-Z~800 nm in rats: survival, morbidity, histopathology, particle distribution and excretion studies (part IV)
Int J Nanomedicine. 2019 ;14 :1163-1175
PMID: 30863052    PMCID: PMC6391148   
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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.
1178-2013 Barone, Frank C Marcinkiewicz, Cezary Li, Jie Feng, Yi Sternberg, Mark Lelkes, Peter I Rosenbaum-Halevi, David Gerstenhaber, Jonathan A Feuerstein, Giora Z Journal Article New Zealand Int J Nanomedicine. 2019 Feb 14;14:1163-1175. doi: 10.2147/IJN.S189048. eCollection 2019.