Unnecessary exposure to ionizing radiation(IR)often causes acute and chronic oxidative damages to normal cells and organs,leading to serious physiological and even life-threatening consequences.Amifostine(AMF)is a val...Unnecessary exposure to ionizing radiation(IR)often causes acute and chronic oxidative damages to normal cells and organs,leading to serious physiological and even life-threatening consequences.Amifostine(AMF)is a validated radioprotectant extensively applied in radiation and chemotherapy medicine,but the short half-life limits its bioavailability and clinical applications,remaining as a great challenge to be addressed.DNAassembled nanostructures especially the tetrahedral framework nucleic acids(tFNAs)are promising nanocarriers with preeminent biosafety,low biotoxicity,and high transport efficiency.The tFNAs also have a relative long-term maintenance for structural stability and excellent endocytosis capacity.We therefore synthesized a tFNA-based delivery system of AMF for multi-organ radioprotection(tFNAs@AMF,also termed nanosuit).By establishing the mice models of accidental total body irradiation(TBI)and radiotherapy model of Lewis lung cancer,we demonstrated that the nanosuit could shield normal cells from IR-induced DNA damage by regulating the molecular biomarkers of anti-apoptosis and anti-oxidative stress.In the accidental total body irradiation(TBI)mice model,the nanosuit pretreated mice exhibited satisfactory alteration of superoxide dismutase(SOD)activities and malondialdehyde(MDA)contents,and functional recovery of hematopoietic system,reducing IRinduced pathological damages of multi-organ and safeguarding mice from lethal radiation.More importantly,the nanosuit showed a selective radioprotection of the normal organs without interferences of tumor control in the radiotherapy model of Lewis lung cancer.Based on a conveniently available DNA tetrahedron-based nanocarrier,this work presents a high-efficiency delivery system of AMF with the prolonged half-life and enhanced radioprotection for multi-organs.Such nanosuit pioneers a promising strategy with great clinical translation potential for radioactivity protection.展开更多
基金supported by National Natural Science Foundation of China(82370929)Sichuan Science and Technology Program(2022NSFSC0002 and 2024NSFSC3508)+4 种基金Sichuan Province Youth Science and Technology Innovation Team(2022JDTD0021)Research and Develop Program,West China Hospital of Stomatology Sichuan University(RD03202302,RCDWJS2024-1)China Postdoctoral Science Foundation(GZB2023470)Sichuan Province Innovative Talent Funding Project for Postdoctoral Fellows(BX202317)The authors would like to thank Dr.Chenghui Li(Analytical&Testing Center,Sichuan University)for technical assistance in assisting with the particle size analysis.
文摘Unnecessary exposure to ionizing radiation(IR)often causes acute and chronic oxidative damages to normal cells and organs,leading to serious physiological and even life-threatening consequences.Amifostine(AMF)is a validated radioprotectant extensively applied in radiation and chemotherapy medicine,but the short half-life limits its bioavailability and clinical applications,remaining as a great challenge to be addressed.DNAassembled nanostructures especially the tetrahedral framework nucleic acids(tFNAs)are promising nanocarriers with preeminent biosafety,low biotoxicity,and high transport efficiency.The tFNAs also have a relative long-term maintenance for structural stability and excellent endocytosis capacity.We therefore synthesized a tFNA-based delivery system of AMF for multi-organ radioprotection(tFNAs@AMF,also termed nanosuit).By establishing the mice models of accidental total body irradiation(TBI)and radiotherapy model of Lewis lung cancer,we demonstrated that the nanosuit could shield normal cells from IR-induced DNA damage by regulating the molecular biomarkers of anti-apoptosis and anti-oxidative stress.In the accidental total body irradiation(TBI)mice model,the nanosuit pretreated mice exhibited satisfactory alteration of superoxide dismutase(SOD)activities and malondialdehyde(MDA)contents,and functional recovery of hematopoietic system,reducing IRinduced pathological damages of multi-organ and safeguarding mice from lethal radiation.More importantly,the nanosuit showed a selective radioprotection of the normal organs without interferences of tumor control in the radiotherapy model of Lewis lung cancer.Based on a conveniently available DNA tetrahedron-based nanocarrier,this work presents a high-efficiency delivery system of AMF with the prolonged half-life and enhanced radioprotection for multi-organs.Such nanosuit pioneers a promising strategy with great clinical translation potential for radioactivity protection.
