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

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-1 alpha (HIF-1 alpha) 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.

Automated summary

In this study, dual-drug nanoparticles were prepared to overcome the drug resistance and poor antimetastatic effects in osteosarcoma treatment. The AD@PLGA-PEG NPs, containing albendazole and doxorubicin, showed enhanced intracellular reactive oxygen species and apoptosis efficiency compared to free DOX. Importantly, ABZ also inhibited the expression of HIF-1α and VEGF, leading to effective inhibition of tumor metastasis. Overall, the AD@PLGA-PEG NPs delivery system provided promising antitumor and antimetastatic efficacy for osteosarcoma.