Fe_(3)O_(4)磁性纳米药物用于克服肿瘤多药耐药性的研究  

Study on Fe_(3)O_(4)-based Magnetic Nanomedicine for Overcoming Multidrug Resistance in Cancer

作　　者：唐昭敏 田维君 TANG Zhaomin(TIAN Weijun School of New Energy and Materials,Southwest Petroluem University,Chengdu 610500,China)

机构地区：[1]西南石油大学新能源与材料学院,成都610500

出　　处：《材料导报》2023年第15期46-52,共7页Materials Reports

基　　金：国家自然科学基金(51803174)。

摘　　要：肿瘤多药耐药性(MDR)是癌症化疗的主要障碍。因此,研发能克服MDR的药物传递系统显得尤为必要。本工作设计了一种以Fe_(3)O_(4)为载体的磁性纳米药物Fe_(3)O_(4)@PDA-TPP/S 2-PEG-hyd-DOX(Fe_(3)O_(4)-ATSPD),采用化疗协同光热疗法(PTT)联合克服肿瘤的多药耐药性。该纳米药物在血液循环中表现出很高的稳定性,能通过磁靶向增强实体瘤的高通透性和滞留效应(EPR)在肿瘤部位富集,从而提高抑瘤率。当肿瘤细胞吞噬纳米药物后,在胞内酸性条件下,Fe_(3)O_(4)-ATSPD释放出抗肿瘤药物DOX进入细胞核。同时,在高浓度谷胱甘肽(GSH)作用下断裂二硫键,暴露出线粒体靶向基团三苯基膦(TPP)改性的光热剂Fe_(3)O_(4)-AT。使用近红外光(NIR)照射肿瘤组织时,线粒体中的Fe_(3)O_(4)-AT快速产生光热效应,扰乱线粒体功能。体内外实验结果表明,化疗协同光热治疗具有最佳的抗肿瘤效果和安全性。Multidrug resistance(MDR)of tumor is a major obstacle to the treatment of cancer.Therefore,it is necessary to develop a drug delivery system that can overcome MDR.In this work,a magnetic nanomedicine Fe_(3)O_(4)@PDA-TPP/S 2-PEG-hyd-DOX(Fe_(3)O_(4)-ATSPD)was designed,and chemotherapy combined with photothermal therapy(PTT)was used to overcome MDR of tumor.This nanomedicine shows high stability in blood circulation,and can be accumulated at the tumor site through the magnetic targeting enhanced high permeability and retention effect(EPR).When intracellular uptake by tumor cells,DOX is released from Fe_(3)O_(4)-ATSPD under acidic condition.Meanwhile,the disulfide bond is broken with the high concentration of glutathione(GSH),exposing the targeting group of triphenylphosphine(TPP)modified photothermal agent Fe_(3)O_(4)-AT.After near-infrared light(NIR)irradiation,the photothermal effect is generated quickly,leading to the mitochondrial dysfunction.The experimental results in vitro and in vivo show that chemotherapy combined with PTT has the best antitumor effect and safety.

关 键 词：多药耐药 线粒体靶向 近红外照射 肿瘤治疗 

分 类 号：R730.53[医药卫生—肿瘤]