| Objective: To develop a novel and stable cell nucleus targeting nanomaterialC60(OH)24-SLN-E as a radioprotective and therapeutic drug with lower toxicity for thenuclear terrorist event，nuclear and radiation accidents as well as the protection ofnormal tissue in patients with radiotherapy.Methods:(1) C60(OH)24-SLN-E was prepared according to the methodestablished in our laboratory and the particle size was measured by laser particle sizeanalyzer. The morphology was observed by Scanning Electron Microscope.(2)Theacute toxicity of the C60(OH)24-SLN-E was evaluated in35SPF ICR mice injectedintraperitoneally (i.p.) with three doses (50,5,0.5μg/kg) separately. The survivalsituation, body weight and peripheral blood cell were observed in30days, and thepathological changes of main organs were observed at the30thday after irradiation.(3)The protective efficiency of the C60(OH)24-SLN-E compared with free C60(OH)24wasinvestigated in a group of40SPF ICR mice (male) exposed to a sub-lethal dose ofwhole body60Co γ-irradiation, which was pretreated with C60(OH)24-SLN-E for7days(daily,100μg/kg i.p.). The survival situation, body weight of the treated mice wasobserved once a day after IR. At the14thday after IR, all mice were sacrificed andperipheral blood was taken for hematological parameter analysis, and the main organswere taken for pathological observation.(4) The therapeutic efficiency of theC60(OH)24-SLN-E compared with free C60(OH)24was evaluated in a group of40SPFICR mice (male) irradiated previously with a sub-lethal dose of whole body60Co γ-irradiation. From24hours after IR, the irradiated mice were treated withC60(OH)24-SLN-E for7days (daily,100μg/kg i.p.), and the survival situation, bodyweight of the treated mice was observed once a day during the experiment, at the21stday after IR, mice were sacrificed and peripheral blood was taken for hematologicalparameter analysis, and the main organs were taken for pathological observation too.Results:(1) The average particle size of C60(OH)24-SLN-E was82.90nm, and itsappearance was spherical shape containing of many C60(OH)24particles.(2) In the acutetoxicity experiment, no died mice was observed, the body weight and peripheral bloodcells of treated mice in different dose groups had no significant difference (p>0.05). Theobvious pathological changes had not been observed in major organs such as liver,kidney, bone marrow and brain in all treated mice. It was confirmed thatC60(OH)24-SLN-E had no acute toxicity to mice below the dose of100μg/kg.(3)Compared with free C60(OH)24, the C60(OH)24-SLN-E pretreated before IR showedthe more efficient preventive effect on the irradiated mice. The weight losing and thedecreasing of WBC and LYM in peripheral blood have been controlled in the treatedmice, the injury of main organs such as spleen, testis, small intestine, lung and spleeninduced by60Co γ radiation has not been observed in the pretreated mice, it showed thepreventive role of radiation damage.(4) Compared with free C60(OH)24, theC60(OH)24-SLN-E injected after IR has more efficient therapeutical effect on theirradiated mice, although it had been injected at the24hours after irradiation. Theweight losing and the decreasing of WBC and LYM in peripheral blood have been curedin the treated mice, the injury of main organs such as spleen, testis, small intestine, lungand spleen induced by60Co γ radiation has not been observed in the treated mice, itshow the powerful therapeutic action on the radiation damage.Conclusion: A novel and stable nanomaterial C60(OH)24-SLN-E with lowertoxicity has been developed successfully. It has shown the role of both higher efficientpreventive effect and powerful therapeutic action on the irradiation damage, whichmaybe a potential stockpiling anti-radiation drug for confronting to the nuclear terroristevent，nuclear and radiation accidents as well as the protection of normal tissue in patients with radiotherapy. |
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