Dual inhibition of glucose uptake and energy supply synergistically restrains the growth and metastasis of breast cancer

Metastatic breast cancer (MBC) is one of the most common and knotty diseases in female population which could place them in a life-threatening condition. For malignant proliferation and migration, can-cer cells require a large amount of glucose and energy to meet the demand of rapid metabolism. Hence, efficiently diminishing the utilization of energy substances by cancer cells is emerging as validated ther-apeutic strategies for cancer therapy. Herein, a nanoplatform with dual-inhibition of glucose uptake and oxidative phosphorylation (OXPHOS) was designed, which consisted of albendazole (ABZ) and atovaquone (ATO) by simple carrier-free self-assembling. The introduction of ABZ could evidently decrease glucose uptake to reduce the main "energy fuel" of cancer cells. Meanwhile, as a blocker of OXPHOS, ATO would reduce adenosine triphosphate (ATP) production and ameliorate hypoxia microenvironment by suppress-ing mitochondrial respiratory chain. Under such dual inhibition of energy metabolism, AA NPs exerted synergistic energy exhaustion effect and outstanding hypoxia improvement function, efficiently inhibit-ing tumor growth and metastasis. This research not only illustrates the feasibility of energy metabolism therapy by co-inhibiting glucose uptake and OXPHOS, but also provides an ingenious tactic to diminish metastasis during MBC treatment (c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.