Low-Temperature Trigger Nitric Oxide Nanogenerators for Enhanced Mild Photothermal Therapy

Surmounting the restriction issues of nitric oxide (NO) delivery to realize their precious on-demand release is highly beneficial for the widespread deployment of gas therapy for application in biomedicine. Herein, by employing core-shell structure Au@SiO₂ nanomaterials with high photothermal performance, a novel strategy was proposed by integrating photothermal conversion nanomaterials and heat-triggered NO donors (RSNO) into a nanoplatform, which achieved photothermal therapy (PTT)-enhanced NO gas therapy under near-infrared (NIR) radiation. Specifically, 2-phenylethynesulfonamide (PES), an inhibitor of heat shock protein 70 (HSP-70), was loaded into the NO nanogenerators to realize effective low-temperature (∼45 °C) PTT. The obtained results showed that the near-infrared radiation (NIR) mediated mild PTT and gas therapy by releasing NO showed a substantially improved synergistic effect based on in vitro and in vivo results in breast cancer (MCF-7) models. Our study points out a strategy to realize mild photothermal therapy by inhibiting the expression of HSP-70 and simultaneously providing an avenue to achieve controllable release of NO. More important, this research highlights the great potential of multifunctional therapeutic agents in the synergistic treatment of cancer.