Tumor-homing, pH- and ultrasound-responsive polypeptide-doxorubicin nanoconjugates overcome doxorubicin resistance in cancer therapy
Tumor-homing, pH- and ultrasound-responsive polypeptide-doxorubicin nanoconjugates overcome doxorubicin resistance in cancer therapy
复制标题
肿瘤归巢、pH 和超声响应的多肽-阿霉素纳米缀合物克服了癌症治疗中的阿霉素耐药性
DOI：
10.1016/j.jconrel.2017.08.017
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发表时间：
2017-10-28
影响因子：
10.8
通讯作者：
Gao, Weiping
中科院分区：
文献类型：
--
作者：
Wang, Zhuoran;He, Qiong;Gao, Weiping
纳米药物有望克服癌症治疗中的耐药性，但体内治疗效果受到其低效的肿瘤靶向，肿瘤渗透性差，细胞摄取低和药物释放不足的限制。在这里，我们报告肿瘤归巢，pH值和超声响应多肽-阿霉素纳米共轭物克服阿霉素耐药性。这些纳米缀合物显示加速的细胞摄取和多柔比星释放，因此当暴露于超声时增强对多柔比星抗性癌细胞的细胞毒性。在阿霉素耐药乳腺癌小鼠模型中，它们在暴露于超声后表现出改善的肿瘤积聚和渗透。更重要的是，它们显示出显著改善的体内抗癌功效，而在超声照射后没有明显的副作用。这些发现表明，这些纳米缀合物作为一类新型智能纳米药物，有望克服癌症治疗中的耐药性。
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.