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

Abstract

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.

Identification of microtubule-associated biomarker using machine learning methods in osteonecrosis of the femoral head and osteosarcoma

“…These shared genes are implicated in various biological processes, including response to hypoxia/oxygen levels, mononuclear cell differentiation, regulation of T cell differentiation, positive regulation of cell adhesion, and response to nutrient levels. OS and ONFH typically occur within bone tissue, and the ischemic hypoxic conditions of bone tissue may be closely related to their pathogenesis [ [28] , [29] , [30] , [31] ]. Under hypoxic conditions, cells may undergo metabolic and behavioral changes, thus affecting tumor cell proliferation, metastasis, and bone tissue repair.…”

Immunotherapy Innovations in the Fight against Osteosarcoma: Emerging Strategies and Promising Progress

“…Nanoparticles -Induced OS-TME is effective in transforming the TME. Np incorporating both albendazole (ABZ) and doxorubicin were designed, and the ABZ component of these nanoparticles demonstrated effective suppression of the expression of HIF-1α and its downstream protein VEGF [ 207 ]. In this study, the combination of ABZ with DOX drastically increases intracellular reactive oxygen species (ROS) and thus elevates tumor cell apoptosis.…”

“…In this study, the combination of ABZ with DOX drastically increases intracellular reactive oxygen species (ROS) and thus elevates tumor cell apoptosis. More significantly, ABZ effectively suppresses the expression of its downstream vascular endothelial growth factor (VEGF) via downregulating the levels of hypoxia-inducible factor-1α (HIF-1α) [ 207 ]. It is worth to mention that MDSCs contribute to bone resorption by activating osteoclasts in an HIF-1α-dependent manner [ 14 ].…”

Engineered nanomaterials enhance drug delivery strategies for the treatment of osteosarcoma

“…Poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs) have been widely used in nanomedicine and regenerative medicine due to their biocompatibility ( Xia et al, 2022b ; Xia et al, 2023 ). Zhao et al (2023a) fabricated AD@PLGA-PEG NPs with PLGA–PEG loads ABZ and DOX (ABZ and DOX molar ratio of 4:1) ( Figure 2A ). ABZ combined with DOX increases intracellular ROS and induces more tumor cell apoptosis compared to free DOX ( Figure 2B ) ( Baldini et al, 1992 ).…”

“…(E) Tumor weights in different treatment groups. Reproduced with permission from ( Zhao T.-T. et al, 2023a ).…”