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.
作者
廖星男
李嘉咪
邓凯
龙清云
黄世文
徐海波
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)
出处
《甘肃农业大学学报》
CAS
CSCD
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)。
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
oxidation-responsive
sonodynamic therapy
chemotherapy
controlled drug release
thioketal
