Nanomedicine-enabled disruption of glucose metabolism and synergistic antitumor therapy

Tumor cells exploit glucose metabolic reprogramming, most notably the Warburg effect of aerobic glycolysis to fuel rapid proliferation, biosynthetic precursor production, and immunosuppressive microenvironment formation. While this creates therapeutic vulnerabilities, conventional metabolic inhibitors face critical limitations in systemic toxicity, metabolic heterogeneity, and inadequate tumor accumulation. Hence, this review details how nanomedicines overcome these limitations through active targeting, enhanced tumor accumulation, stimuli-responsive drug release, and co-delivering multiple drugs for combination therapy. Guided by the glucose metabolic cascade, we comprehensively discuss nano-enabled strategies to achieve antitumor efficacy through inhibiting glucose transportation, blocking glucose supply, accelerating glucose depletion, suppressing glycolytic enzymes, and concurrently inhibiting oxidative phosphorylation. Furthermore, this review summarizes strategies leveraging nanomedicines to integrate glucose metabolism modulation with complementary therapies, such as immunotherapy, radiochemotherapy, cuproptosis induction, and photothermal therapy, for synergistically eradicating tumors. Recognizing glucose metabolism reprogramming as a pivotal therapeutic target in oncology, we emphasize the indispensable role of nanomedicine in overcoming persistent barriers to advance tumor-selective metabolic intervention, thereby elevating treatment efficacy and accelerating the clinical translation of precision nanotherapeutics.