State Key Laboratory of Ultrasound Engineering in Medicine Co-Founded by Chongqing & the Ministry of Science & Technology, College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China.
Nanomedicine (Lond). 2018 May;13(9):981-996. doi: 10.2217/nnm-2017-0375. Epub 2018 Mar 14.
To build up a combined therapy strategy to address limitations of the enhanced permeability and retention (EPR) effect and improve the efficiency of tumor therapy.
MATERIALS & METHODS: A pH-sensitive nanocomplex for co-delivery of doxorubicin (DOX) and all-trans retinoic acid (ATRA) was developed based on nanodiamonds (DOX/ATRA-NDs) to enhance intracellular retention of drugs. Meanwhile, ultrasound was employed to enhance tumor vascular penetration of DOX-ATRA-NDs.
The distribution of DOX/ATRA-NDs in the tumor tissues increased threefold when ultrasound was applied at 1 MHz and 0.6 W/cm. Comparing with unmodified chemotherapeutics, the combined therapy induced more tumor cells apoptosis and greater tumor growth inhibition in both liver and breast tumor models.
DOX-ATRA-NDs demonstrate great potential in clinical applications.
构建联合治疗策略以解决增强型通透性和保留（EPR）效应的局限性，并提高肿瘤治疗的效率。
基于纳米金刚石（DOX/ATRA-NDs）构建了一种用于共递送多柔比星（DOX）和全反式视黄酸（ATRA）的 pH 敏感的纳米复合物，以增强药物的细胞内保留。同时，采用超声增强 DOX-ATRA-NDs 的肿瘤血管穿透性。
当以 1MHz 和 0.6W/cm 的频率应用超声时，DOX/ATRA-NDs 在肿瘤组织中的分布增加了三倍。与未修饰的化疗药物相比，联合治疗在肝肿瘤和乳腺肿瘤模型中诱导了更多的肿瘤细胞凋亡和更大的肿瘤生长抑制。
DOX-ATRA-NDs 在临床应用中具有很大的潜力。
