State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing 210009, China.
Mol Pharm. 2023 May 1;20(5):2612-2623. doi: 10.1021/acs.molpharmaceut.3c00068. Epub 2023 Apr 12.
Chemotherapy is the main treatment method for osteosarcoma in the clinic. However, drug resistance and its poor antimetastatic effects greatly limit its clinical application. In this work, dual-drug nanoparticles (NPs) containing albendazole (ABZ) and doxorubicin (DOX), named AD@PLGA-PEG NPs, were prepared to solve the problems of chemotherapeutic drug resistance and poor antimetastasis effects. Compared with free DOX, ABZ combined with DOX can increase intracellular reactive oxygen species (ROS) and induce more tumor cell apoptosis; therefore, AD@PLGA-PEG NPs produced more mitochondria-mediated oxidative stress and better apoptosis efficiency. Importantly, ABZ can also effectively inhibit the expression of hypoxia inducible factor-1α (HIF-1α) and then reduce the expression of its downstream vascular endothelial growth factor (VEGF); thus, the AD@PLGA-PEG NPs effectively inhibited tumor metastasis in vivo. Collectively, the dual-drug AD@PLGA-PEG NPs delivery system provided prominent antitumor and antimetastatic efficacy and might be a promising treatment for osteosarcoma.
化疗是临床治疗骨肉瘤的主要方法。然而，药物耐药性及其较差的抗转移作用极大地限制了其临床应用。在这项工作中，制备了含有阿苯达唑（ABZ）和多柔比星（DOX）的双药纳米粒子（NPs），命名为 AD@PLGA-PEG NPs，以解决化疗药物耐药性和较差的抗转移作用的问题。与游离 DOX 相比，ABZ 与 DOX 联合使用可以增加细胞内活性氧（ROS）并诱导更多的肿瘤细胞凋亡；因此，AD@PLGA-PEG NPs 产生更多的线粒体介导的氧化应激和更好的凋亡效率。重要的是，ABZ 还可以有效抑制缺氧诱导因子-1α（HIF-1α）的表达，从而降低其下游血管内皮生长因子（VEGF）的表达；因此，AD@PLGA-PEG NPs 有效地抑制了体内肿瘤转移。综上所述，双药 AD@PLGA-PEG NPs 递药系统提供了显著的抗肿瘤和抗转移疗效，可能是治疗骨肉瘤的一种有前途的方法。
