目的 探究超声-微泡介导的miR-128通过调节PTEN对乳腺癌细胞阿霉素耐药的影响。方法 qPCR检测miR-128在乳腺癌细胞系中的表达,并利用结合微泡的miR-128质粒(质粒+超声+SF6微泡)转染细胞,探究超声-微泡介导的miR-128对乳腺癌细胞阿霉素耐药的影响。CCK8实验检测乳腺癌细胞的活性;qPCR检测过表达miR-128后对PTEN的影响和对乳腺癌细胞阿霉素耐药的影响。结果 miR-128在阿霉素耐药乳腺癌细胞中低表达;过表达miR-128能够增加乳腺癌细胞对阿霉素的敏感性,超声-微泡介导的miR-128进一步增强了乳腺癌细胞对阿霉素的敏感性;miR-128通过调节PTEN从而促进乳腺癌细胞对阿霉素耐药。结论 miR-128过表达可以增强乳腺癌对阿霉素的敏感性,超声-微泡介导的miR-128进一步增强了乳腺癌细胞对阿霉素的敏感性,本研究为乳腺癌阿霉素耐药的治疗提供了新的分子靶标和治疗途径。

Objective To explore the effect of ultrasound-microbubble mediated miR-128 on doxorubicin resistance in breast cancer cells by regulating PTEN. Methods Quantitatine PCR (qPCR) was used to detect the expression of miR-128 in breast cancer cell lines, and the ultrasound-microbubble combined miR-128 plasmid(plasmid+ultrasound+SF6 microbubbles) was used to transfect the cells to explore the effects of ultrasound-microbubble mediated miR-128 on doxorubicin resistance in cancer cells. The CCK8 experiment was used to detect the activity of breast cancer cells; qPCR was used to detect the effect of overexpression of miR-128 on PTEN and the effect on doxorubicin resistance of breast cancer cells. Results miR-128 was under-expressed in doxorubicin-resistant breast cancer cells; overexpression of miR-128 increased the sensitivity of breast cancer cells to doxorubicin,ultrasound-microbubble mediated miR-128 further enhanced breast cancer cells sensitivity to doxorubicin; miR-128 promote resistance to doxorubicin in breast cancer cells by regulating PTEN. Conclusion Overexpression of miR-128 could enhance the sensitivity of breast cancer to doxorubicin. Ultrasound-microbubble mediated miR-128 further enhanced the sensitivity. This study provided a treatment for doxorubicin resistance in breast cancer with new molecular targets and therapeutic approaches.

与正常组织细胞微环境相比,肿瘤微环境具有一定的异质性,包括偏酸性、氧化还原状态失衡、存在高浓度活性氧以及酶过量表达等。根据以上肿瘤微环境特点,可设计出一系列通过各种特殊微环境响应型连接臂相连的小分子或聚合物前药纳米粒。其中,多柔比星阿霉素作为一类最常见的广谱抗肿瘤药物在治疗肿瘤的过程中发挥重要作用。文章探讨了在肿瘤微环境特异性的生理状态下针对不同微环境所设计的多柔比星前药及其释放特性等,归纳总结了肿瘤微环境响应型多柔比星前药的研究进展。

Compared with normal tissue cell microenvironment, there is some differences in tumor microenvironment, such as partial acidity, imbalance of redox state, high concentration of reactive oxygen species and cathepsin. According to the above characteristics of tumor microenvironment, a series of small molecule or polymer prodrug nanoparticles connected by various special microenvironment responsive structures can be designed. Doxorubicin, as one of the most common broad-spectrum antitumor drugs, plays an important role in the treatment of tumors. This review discusses the doxorubicin prodrug designed for different tumor microenvironments under the physiological state of tumor microenvironment specificity and their release characteristics, and summarizes the research progress of tumor microenvironment-responsive doxorubicin prodrug.

       目的   初步探讨可注射型载阿霉素水凝胶对胶质瘤的治疗作用。方法   使用透析法检测载阿霉素水凝胶在体外释放药物的情况。构建大鼠皮下C6胶质瘤模型，按不同给药途径分为空白对照组、经静脉注射组、水凝胶组。给药15 h后，经免疫荧光检测阿霉素在肿瘤内部的分布情况。给药7 d后，计算出各组的抑瘤率；并对肿瘤组织进行苏木精-伊红染色。结果   在体外，载阿霉素水凝胶具有缓释药物的性能。在体内，与经静脉给药相比，局部注射载阿霉素水凝胶使瘤内分布更多阿霉素，抑瘤率更高（42% vs 64%），肿瘤细胞坏死更明显。结论   载阿霉素水凝胶可为胶质瘤局部化学治提供新的载体。

      Objective  To investigate the therapeutic effect of injectable doxorubicin-containing hydrogel on glioma．Methods  The release of doxorubicin hydrogel in vitro was detected by dialysis．The subcutaneous C6 glioma model of  rats was constructed and divided into blank control group，intravenous injection group and hydrogel group according to different administration methods．The distribution of doxorubicin in the tumor was detected by immunofluorescence 15 hours after administration．After 7 days of administration，the tumor inhibition rate of each group was calculated．The tumor tissue was stained with hematoxylin eosin．Results  In vitro，doxorubicin-containing hydrogels had sustained drug release properties．In vivo，compared with intravenous administration，local injection of doxorubicin-containing hydrogel resulted in more doxorubicin distribution，higher tumor inhibition rate（42% vs 64%）and more obvious tumor cell necrosis．Conclusions  Doxorubicin-containing hydrogel can provide a new carrier 

for local chemotherapy of glioma．