Hypoxia Inhibitor Combined with Chemotherapeutic Agents for Antitumor and Antimetastatic Efficacy against Osteosarcoma

• Published in: Molecular pharmaceutics 2023-05, Vol.20 (5), p.2612-2623
• Main Authors: Zhao, Tian-Tian, Zhou, Tian-Jiao, Zhang, Chen, Liu, Ying-Xuan, Wang, Wen-Jia, Li, Chengjun, Xing, Lei, Jiang, Hu-Lin
• Format: Article
• Language: English
• Subjects: Bone Neoplasms - drug therapy; Cell Line, Tumor; Doxorubicin - pharmacology; Doxorubicin - therapeutic use; Humans; Hypoxia; Nanoparticles; Osteosarcoma - drug therapy; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.3c00068

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.