Starvation therapy-amplified photothermal therapy against colorectal cancer via GLUT1-mediated energy deprivation

Photothermal therapy (PTT) has come into view as an innovative strategy for colorectal cancer (CRC) therapy based on its exceptional spatial selectivity and minimal side effects. However, clinical PTT is severely restricted due to the limited depth of laser penetration and the self-protective nature of cells with heat shock protein (HSP) upregulation. Herein, we prepared a synergistic PTT/ST near-infrared (NIR) nanoplatform (PR NPs), which is self-assembled from the NIR phototherapeutic agent PPAB and the glucose transporter 1 (GLUT1) inhibitor resveratrol (RES) to fight CRC. The PR NPs display enhanced cancer PTT efficiency owing to the downregulation of adenosine triphosphate (ATP)-dependent HSPs mediated by RES. Meanwhile, the enhanced metabolism and energy consumption triggered by PTT further exacerbate the energy crisis, amplifying the starvation therapy (ST) effect. More significantly, the RES released from PR NPs can also specifically target GLUT1 in CRC cells to promote apoptosis and suppress migration. Hence, the versatile NIR PR NPs can simultaneously enable efficient photothermal ablation and precise energy deprivation to improve antitumor outcome, providing a novel paradigm for CRC treatment.