氧化响应性阿霉素前药胶束在声动力-化学疗法联合治疗癌症中的应用  

Oxidation-responsive DOX prodrug nanomicelles application in the combined sonodynamic-chemotherapy of cancer

作　　者：廖星男 李嘉咪 邓凯[1] 龙清云[1] 黄世文[2] 徐海波[1] LIAO Xingnan;LI Jiami;DENG Kai;LONG Qingyun;HUANG Shiwen;XU Haibo(Department of Radiology,Zhongnan Hospital of Wuhan University,Wuhan University,Wuhan 430071,China;Key Laboratory of Biomedical Polymers of Ministry of Education,Department of Chemistry,Wuhan University,Wuhan 430072,China)

机构地区：[1]武汉大学中南医院医学影像科,湖北武汉430071 [2]武汉大学化学与分子科学学院生物医学高分子材料教育部重点实验室,湖北武汉430072

出　　处：《甘肃农业大学学报》2022年第5期37-44,共8页Journal of Gansu Agricultural University

基　　金：湖北省自然科学基金项目(2021CFB055);中央高校基本科研业务费专项资金-自主科研项目(2042021kf0153)。

摘　　要：【目的】探究超声触发氧化响应性阿霉素(DOX)纳米前药对肿瘤的抑制效果,为癌症患者提供安全的声动力与化学疗法联合治疗方法。【方法】制备具有单线态氧(1O2)特异性响应性DOX前药胶束(PTDOX-M)和无响应性DOX前药胶束(PCDOX-M)。以2种前药胶束为基础,在细胞和动物水平研究癌症声动力-化疗治疗疗效。【结果】溶液中,超声作用下,DOX产生的1O2无法触发PCDOX-M中的DOX释放,而PTDOX-M中的DOX释放量在12 h达到42%。在无超声处理下,PTDOX-M中无DOX释放。体内研究发现,超声触发下,PTDOX-M对4T1皮下移植瘤子的抑制率是PCDOX-M的3.2倍。【结论】超声作用下,PTDOX-M可以在局部释放化疗药物DOX,以此介导的声动力-化学疗法联合作用显著抑制了肿瘤生长,有望避免对正常组织造成损伤,为癌症治疗提供安全高效的方法。【Objective】The study aimed to test the inhibiting effect of an oxidation-responsive DOX prodrug nanomicelles trigged by ultrasound(US)irradiation in the therapy of cancer,exploring a safe and effective method of combined sonodynamic-chemotherapy for cancer therapy.【Method】The oxidationresponsive DOX prodrug(PTDOX-M)and non-responsive DOX prodrug(PCDOX-M)were developed and their curative effect were determined in the combined sonodynamic-chemotherapy of cancer upon US irradiation in vitro and in vivo.【Result】Upon US irradiation,the 1O2 generated by DOX could not trigger DOX release in PCDOX-M,while the DOX release from PTDOX-M reached 42%in vitro at 12 h.However,there was no DOX released from PTDOX-M without US irradiation.Upon US irradiation,the inhibition rate of PTDOX-M to 4T1 subcutaneous graft tumors in vivo was 3.2 times as high as that of PCDOXM.【Conclusion】Under US irradiation,the PTDOX-M could locally release the DOX,mediated by which the combined sonodynamic-chemotherapy could significantly inhibit tumor growth and resulted in negligible damage to the normal tissues.Therefore,it could be anticipated to serve as a safe and effective method for the therapy of cancer.

关 键 词：氧化响应 声动力治疗 化学疗法 药物可控释放 酮缩硫醇 

分 类 号：R730.[医药卫生—肿瘤]