Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.
Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.
J Control Release. 2017 Oct 28;264:66-75. doi: 10.1016/j.jconrel.2017.08.017. Epub 2017 Aug 31.
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.
纳米药物有望克服癌症治疗中的药物耐药性，但由于其肿瘤靶向效率低、肿瘤穿透性差、细胞摄取率低和药物释放不足，其体内治疗效果受到限制。在这里，我们报告了用于克服多柔比星耐药性的肿瘤归巢、pH 和超声响应性多肽-多柔比星纳米复合物。当暴露于超声时，这些纳米复合物显示出加速的细胞摄取和多柔比星释放，从而增强了对多柔比星耐药癌细胞的细胞毒性。在多柔比星耐药性乳腺癌小鼠模型中，它们在超声暴露后显示出改善的肿瘤积累和穿透。更重要的是，它们在超声照射后显示出显著提高的体内抗癌疗效，而没有明显的副作用。这些发现表明，这些纳米复合物有望成为一种新的智能纳米药物，用于克服癌症治疗中的药物耐药性。
