NIR-Activated Hollow Upconversion Nanocomposites for Tumor Therapy via GLUT1 Inhibition and Mitochondrial Function Disruption

Tumor remains a leading contributor to global mortality rates, necessitating urgent advancements in therapeutic interventions. Due to the intricate nature of the tumor microenvironment, individual differences make it difficult to achieve desired efficacy with a single strategy. To overcome these challenges, we develop for the first time hollow NaBiF₄-based nanocomposites NaBiF₄-W/R-D for tumor therapy by glucose transporter 1 (GLUT1) inhibition and mitochondrial function disruption. NaBiF₄-W/R-D can inhibit GLUT1 function due to the presence of WZB117, which leads to a decrease in intracellular glucose in tumor cells, leaving them in a starved state. Meanwhile, the upconversion luminescence of NaBiF₄-W/R-D under near-infrared (NIR) laser irradiation can stimulate the photosensitizer to efficiently generate singlet oxygen to disrupt the mitochondrial function and then kill the tumor cells. In addition, NIR-II emission from NaBiF₄-W/R-D is used for fluorescence imaging to determine the optimal time point for tumor treatment. Finally, NaBiF₄-W/R-D leads to mitochondrial membrane potential depolarization, impaired mitochondrial function, activation of caspase-3, and ultimately the amplification of apoptosis.