Suppression of tumor energy supply by liposomal nanoparticle-mediated inhibition of aerobic glycolysis.

Aerobic glycolysis enables cancer cells to rapidly take up nutrients (e.g., nucleotides, amino acids, lipids) and incorporate them into the biomass needed to produce a new cell. In contrast to existing chemotherapy/radiotherapy strategies, inhibiting aerobic glycolysis to limit ATP yield is a highly efficient approach for suppressing tumor cell proliferation. However, most, if not all, current inhibitors of aerobic glycolysis cause significant adverse effects, due to their nonspecific delivery and distribution to non-diseased organs, low bioavailability and a narrow therapeutic window. New strategies to enhance the biosafety and efficacy of these inhibitors are needed for moving them into clinical application. To address this need, we developed a liposomal nanocarrier functionalized with a well-validated tumor targeting peptide to specifically deliver the aerobic glycolysis inhibitor 3-bromopyruvate (3-BP) into tumor tissue. The nanoparticles effectively targeted tumors after systemic administration into tumor-bearing mice, and suppressed tumor growth by locally releasing 3-BP to inhibit ATP production of the tumor cells. No overt side effects were observed in the major organs. This report demonstrates the potential utility of the nanoparticle-enabled delivery of an aerobic glycolysis inhibitor as an anticancer therapeutic agent.