Development of a mitochondria-targeted nano-complex of imidazole-substituted oleic acid as a radiomitigator

Details

• Personal Author:
  Amoscato A ; Epperly M ; Greenberger J ; Kagan V ; Kapralov A ; Seo W ; Star A ; Tyurin V ; Tyurina Y ; Amoscato A ; Epperly M ; Greenberger J ; Kagan V ; Kapralov A ; Seo W ; Star A ; Tyurin V ; Tyurina Y
• Description:
  Increasing likelihood of intended or accidental exposure to ionizing radiation dictates the necessity to develop effective medical countermeasures of radiation injury as has been recognized as a high priority both in the US and worldwide. No effective medical radiation countermeasures of acute and delayed radiation injuries are currently known. Based on newly discovered mechanisms of radiation damage - oxidation of cardiolipin by cytochrome c in mitochondria as a required stage in radiation- induced apoptosis - we designed and synthesized mitochondria-targeted triphenylphosphonium-conjugated imidazole-substituted oleic (TPP-OA) which prevented/mitigated cell death induced by irradiation and protected C57BL6 mice against total body irradiation. To improve therapeutic efficiency of TPP-IOA we chose to employ branched polyethylene glycol (PEG) functionalized single walled carbon nanotubes (SWCNT) and use it as a carrier to deliver mitochondria-targeted TPP-IOA to tissues. We found that loading of PEG-SWCNT with TPP-IOA caused a marked extension of the life-span of TPP-IOA in circulation. Moreover we showed that TPP-IOA-nano-complex was more effective as radiomitigator than free TPP-IOA. While the dose of TPP-IOA in TPP-IOA-nano-complexes was two times lower compared with free TPP-IOA the mitigating effect of TPP-IOA-nanocomplexes was higher than that of TPP-IOA alone. Importantly, we were able to detect TPP-IOA nano-complexes in radiosensitive tissue such as small intestine. These data warrant further studies aimed at the development of radioprotectors/radiomitigators with broad spectrum of applications in biomedicine and biodefense. [Description provided by NIOSH]
• Subjects:
  Ethylenes Glycols Laboratories Occupational Health Radiation Radiation Injuries Radiation Protection Safety Toxicology
• Keywords:
  Cell-damage Cellular-function Cellular-reactions Dose-response Intestinal-tissue Ionizing-radiation Laboratory-animals Nanotechnology Radiation-injury Radiation-protection Radiation-therapy Radiobiology Therapeutic-agents Tissue-culture

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary ; Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; OSHA Region 6 ; Pennsylvania ; Texas
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Volume:
  132
• Issue:
  1
• NIOSHTIC Number:
  nn:20042445
• Citation:
  Toxicologist 2013 Mar; 132(1):428
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0) ; Polyethylene glycol (CAS RN 25322-68-3) ; Carbon (CAS RN 7440-44-0) ; Polyethylene glycol (CAS RN 25322-68-3)
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Manufacturing ; Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  False
• Start Date:
  20050701
• Source Full Name:
  The Toxicologist. Society of Toxicology 52nd Annual Meeting and ToxExpo, March 10-14, 2013, San Antonio, Texas
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ed93342e6c75bdb7bc55054355539d69a50caec64fa324bc1e290375cb395d5782197db1f360dc0a1d20357da5c946e4e4d8fb0002b4c152df6a99caee99a0f8
• Download URL:
  https://stacks.cdc.gov/view/cdc/194668/cdc_194668_DS1.pdf
• File Type:
  [PDF - 569.88 KB ]