多肽金纳米粒P12在小鼠体内的生物安全性研究

Biosafety study of peptide gold nanoparticles P12 in mice

目的:探究多肽金纳米粒P12经气道给药后在小鼠体内的生物安全性。方法:将125 nmol/L P12作为初始浓度,采用剂量递增法经小鼠气道给药,通过观察气道给予递增剂量的P12后小鼠1周内每日的临床症状和体质量变化,确认小鼠对P12的最大耐受剂量;经小鼠气道给予50μL治疗剂量(500 nmol/L)和大剂量(2μmol/L)P1224 h后,通过观察小鼠的血常规、血生化指标、脏器系数和组织病理学变化,进一步评价P12的急性毒性,以评估P12的体内安全性。结果:在给药后的1周内,给药量高达治疗剂量的4倍时小鼠的体质量下降也不大于15%,且临床症状表现正常。气道给予治疗剂量或大剂量P1224 h后,小鼠的脏器系数、血常规、血生化和主要脏器的组织病理学切片均表现正常。结论:经小鼠气道给予P12的最大耐受剂量远高于治疗剂量,P12具有较高的生物安全性。

Objective To investigate the biosafety of peptide gold nanoparticles P12 administered via airway in mice.Methods With 125 nmol/L P12 as the initial concentration,the maximum tolerated dose of P12 was confirmed by one-week observing of the daily clinical signs and body mass changes in the mice after airway administration of increasing doses of P12 by the dose-escalation method.The acute toxicity of P12 was further evaluated by observing the changes of blood routine examination,blood biochemical indices,organ coefficients and histopathological signs in mice 24 hours after the administration of 50μL of therapeutic dose(500 nmol/L)and high dose(2μmol/L)of P12 via airway so as to assess the in vivo safety of P12.Results Within 1 week of administration,the mice administered at doses up to 4 times the therapeutic dose showed normal clinical signs while no greater than 15%decrease in body mass.After 24 h of airway administration of therapeutic doses or high doses of P12,the mice showed no significant changes in organ coefficients,blood routine examination,blood biochemical indices and histopathological signs of the major organs.Conclusion The maximum tolerated dose of P12 via the mouse airway is much higher than the therapeutic dose,and thus P12 proves its high biosafety.