Exploiting tumor amino acid metabolic heterogeneity: Biological principles and precision nanomedicine

Amino acid metabolism occupies a central position in tumor biology and cancer therapy. Amino acids are not only fundamental substrates for protein synthesis but also critical metabolic and signaling hubs that regulate energy production, nucleotide biosynthesis, redox homeostasis, and epigenetic programming. Owing to their indispensable roles in bioenergetics, anabolic support, and cellular homeostatic control, amino acid metabolism has become a major focus of contemporary cancer research and targeted intervention. However, despite the therapeutic promise of targeting these metabolic vulnerabilities, clinical translation falters due to poor bioavailability and rapid adaptive rewiring. Nanotechnology bridges this gap by offering precision tools to enhance antitumor efficacy while reducing systemic toxicity: by leveraging tumor-specific amino acid metabolic profiles, nanomedicines with targeted delivery and controllable release can be engineered to increase intratumoral drug exposure, minimize off-target effects, and improve therapeutic outcomes. This review systematically integrates the biological dysregulation of specific amino acids with recent progress in nanomedicine strategies. We discuss biological mechanisms and therapeutic engineering side-by-side for key amino acids, and analyze the major challenges limiting clinical translation, outlining potential directions for future optimization.