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Tumor-homing, pH- and ultrasound-responsive polypeptide-doxorubicin nanoconjugates overcome doxorubicin resistance in cancer therapy
Journal of Controlled Release ( IF 10.8 ) Pub Date : 2017-08-31 , DOI: 10.1016/j.jconrel.2017.08.017
Zhuoran Wang , Qiong He , Wenguo Zhao , Jianwen Luo , Weiping Gao

Nanomedicines hold promise in overcoming drug resistance in cancer therapy, but the in vivo therapeutic efficacy is limited by their inefficient tumor targeting, poor tumor penetration, low cellular uptake and insufficient drug release. Here we report tumor-homing, pH- and ultrasound-responsive polypeptide-doxorubicin nanoconjugates for overcoming doxorubicin resistance. These nanoconjugates show accelerated cellular uptake and doxorubicin release and thus enhanced cytotoxicity to doxorubicin-resistant cancer cells when exposed to ultrasound. In a doxorubicin-resistant breast cancer mouse model, they exhibited improved tumor accumulation and penetration following exposure to ultrasound. More importantly, they displayed significantly improved in vivo anticancer efficacy without appreciable side effects post ultrasound irradiation. These findings suggest that these nanoconjugates are promising as a new class of intelligent nanomedicines for overcoming drug resistance in cancer therapy.



中文翻译:

肿瘤归巢,pH和超声响应多肽-阿霉素纳米复合物在癌症治疗中克服了对阿霉素的耐药性

纳米药物有望克服癌症治疗中的耐药性,但是体内治疗功效受到其无效的肿瘤靶向,不良的肿瘤渗透性,低的细胞摄取和药物释放不足的限制。在这里我们报告肿瘤归巢,pH和超声响应多肽-阿霉素纳米复合物克服阿霉素抗性。这些纳米共轭物显示出加速的细胞摄取和阿霉素的释放,因此当暴露于超声时对抗阿霉素的癌细胞具有增强的细胞毒性。在抗阿霉素的乳腺癌小鼠模型中,它们在暴露于超声后显示出改善的肿瘤积累和渗透性。更重要的是,它们在超声照射后显示出显着改善的体内抗癌功效,而没有明显的副作用。

更新日期:2017-08-31
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