LAUSR

Although radiotherapy is one of the most common treatments for triple-negative breast cancer (TNBC), it frequently has unsatisfactory therapeutic outcomes due to the radiation resistance of tumor tissues. Therefore, a synergistic strategy is urgently needed to increase therapeutic responses and prolong patient survival. Herein, we constructed gold nanocages (GNCs) loaded with a hyperpyrexia-sensitive nitric oxide (NO) donor (thiolate cupferron) to integrate extrinsic radiosensitization, local photothermal therapy, and near-infrared-activated NO gas therapy. The resulting nanoplatform (GNCs@NO) showed a high photothermal conversion efficiency, which induced the death of cancer cells and facilitated rapid NO release in tumor tissues. The radiosensitizing efficacy of GNCs@NO was further demonstrated in vitro and in vivo. Importantly, the released NO reacted with the reactive oxide species induced by radiotherapy to produce more toxic reactive nitrogen species, exerting a synergistic effect to improve anticancer efficacy. Thus, GNCs@NO demonstrated excellent effects as a combination therapy with few adverse effects. Our work proposes a promising nanoplatform for the radio/photothermal/gas treatment of TNBC.