A DNA tetrahedron-based nanosuit for efficient delivery of amifostine and multi-organ radioprotection  

作　　者：Yuting Yang Jinlong Yang Jianwei Zhu Xingyu Chen Li Zhou Wenjuan Ma Yunfeng Lin 

机构地区：[1]State Key Laboratory of Oral Diseases,National Center for Stomatology,National Clinical Research Center for Oral Diseases,West China Hospital of Stomatology,Sichuan University,Chengdu,Sichuan,610041,PR China [2]Sichuan Provincial Engineering Research Center of Oral Biomaterials,Chengdu,Sichuan,610041,PR China [3]National Center for Translational Medicine,Shanghai Jiao Tong University,Shanghai,200240,PR China [4]Department of Neurosurgery of West China Hospital,Sichuan University,Chengdu,610041,PR China [5]Department of Neurosurgery,Sichuan Provincial People’s Hospital,University of Electronic Science and Technology of Chin1,Chengdu,611731,PR China [6]Histology and Imaging Platform,Core Facility of West China Hospital,Sichuan University,Chengdu,610041,PR China

出　　处：《Bioactive Materials》2024年第9期191-205,共15页生物活性材料（英文）

基　　金：supported by National Natural Science Foundation of China(82370929);Sichuan Science and Technology Program(2022NSFSC0002 and 2024NSFSC3508);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.

摘　　要：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.

关 键 词：Ionizing radiation Nanosuit AMIFOSTINE Tetrahedral framework nucleic acids DNA damage Multi-organ protection Lewis lung cancer model 

分 类 号：TB383[一般工业技术—材料科学与工程]