Targeting Glucose Transporter 1 (GLUT1) in Cancer: Molecular Mechanisms and Nanomedicine Applications
Zhen Ren, Jingyuan Zhao, Shuai Li, Hong Yuan
Abstract
Glucose transporter 1 (GLUT1), a central orchestrator of tumor metabolic reprogramming, sustains malignant progression by enforcing glycolytic dependency and conferring therapeutic resistance. While conventional GLUT1-targeted small-molecule inhibitors demonstrate preclinical efficacy through glucose transport blockade and chemo-radiosensitization, their clinical translation is impeded by intrinsic limitations. Emerging nanomedicine paradigms have redefined GLUT1-targeted interventions through multifunctional platforms that synergistically unify precision therapeutics, imaging guidance, and immunometabolic modulation. Meanwhile, advanced formulations further exploit GLUT1-mediated endocytosis to achieve blood-brain barrier penetration, thus potentially addressing key challenges in the treatment of CNS malignancies. Notably, combinatorial nanoarchitectures simultaneously disrupt metabolic pathways and reprogram immunosuppressive niches via dual-targeting strategies, thereby counteracting tumor adaptation mechanisms. These innovations transcend conventional therapeutic boundaries by establishing metabolic-immune interplay regulation and barrier-defying delivery systems. This review systematically analyses the evolving landscape of GLUT1-targeted nanomedicine, evaluating both traditional molecular inhibitors and next-generation nanoplatforms that harness GLUT1 through diverse modalities. By dissecting molecular mechanisms and translational applications, we elucidate the diagnostic and therapeutic value of GLUT1-targeted nano-strategies in precision oncology while outlining future directions for clinical implementation.