Stress mitigation protects DNA and other healthy cell components from the effects of radiation therapy or radiation-containing weapons.
This invention is a means of radiation protection, or cellular oxidative stress mitigation, via a sequence of quenching radical species using nano-engineered scaffolds, specifically single-wall carbon nanotubes (SWNTs) and their derivatives. The material can be used as a means of radiation protection by reducing the number of free radicals within, or nearby, organelles, cells, tissue, organs, or living organisms, thereby reducing the risk of damage to DNA and other cellular components (i.e., RNA, mitochondria, membranes, etc.) that can lead to chronic and/or acute pathologies, including but not limited to cancer, cardiovascular disease, immuno-suppression, and disorders of the central nervous system. In addition, this innovation could be used as a prophylactic or antidote for accidental radiation exposure, during high-altitude or space travel where exposure to radiation is anticipated, or to protect from exposure from deliberate terrorist or wartime use of radiation-containing weapons.
BHA and BHT are well-known food preservatives that are excellent radical scavengers. These compounds, among others, attached to SWNTs make excellent radical traps. The 4-(2-aminoethyl)- 2,6-bis(1,1-dimethylethyl)phenol (amino-BHT, compound 3, Scheme 1) groups are associated with nano-engineering materials. The amino-BHT groups can be associated with SWNTs that have carboxylic acid groups via acidbase association, or via covalent attachment. The SWNTs can also have poly(ethylene glycol) (PEG) chains associated with them to enhance the solubility of the nano-engineered materials in water and buffered systems. Likewise, 4- ( 2 - c a r b o x y e t h y l ) - 2 , 6 - b i s ( 1 , 1 - dimethylethyl) phenol (carboxy-BHT, compound 4, Scheme 2) can be associated with aminated SWNTs (i.e., SWNTs that are carboxylated, then aminated via interaction with poly(ethylene imine), again via acid base association.
One idea is to attach 2,6-di(tert-butyl) phenols (BHT and BHA analogs) to SWNTs, and to use these as delivery agents to quench large amounts of radicals that can be established in a cell due to oxidative stress or radiation-induced pathways. The tert-butyl groups are most properly named as 1,1-dimethylethyl moieties. Many other radical scavengers can be appended to the sidewalls of water-soluble SWNTs via acid-base, covalent or non-covalent (pi-pi interactions of Van der Waals interactions) functionalized protocols. In some cases, the parent pluronic-wrapped SWNT can show efficacy in this reaction as well. Two other known therapeutic radical scavengers include Lavendustin B and Amifostin. One skilled in the art can think of several permutations for derivatizing radical scavengers to SWNTs or double-wall nanotubes (DWNTs) for multi-wall nanotubes (MWNTs) where there are three or more walls predominating in a sample.
This work was done by James M. Tour, Meng Lu, Rebecca Lucente-Schultz, Ashley Leonard, Condell Dewayne Doyle, Dimitry V. Kosynkin, and Brandi Katherine Price of Rice University for Johnson Space Center.
In accordance with Public Law 96-517, the contractor has elected to retain title to this invention. Inquiries concerning rights for its commercial use should be addressed to:
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