Second Near‐Infrared Light Triggered Mini Plasmonic Heterostructures for Photothermal‐Derived Multimodal Synergistic Cancer Therapy

Abstract Photothermal therapy (PTT) is an emerging treatment tool for cancer therapy. However, its therapeutic outcomes are largely affected by the photophysical properties of photothermal agents and the responses of cancer cells. To reveal the full potential of PTT, in this work, a photothermal‐derived multimodal synergistic therapy is proposed based on mini‐size AuNR@Cu 2‐ x S (mARC) plasmonic heterostructures. Due to the unique optical properties of mARC nanoparticles, a remarkably high heat conversion efficiency of 62% is achieved under a 1064 nm laser. Quercetin, as a heat shock protein inhibitor, is loaded into the cavity of mARC. Interleukin‐8 (IL‐8) siRNA, which regulates the cell proliferation rate, is attached to mARC via electrostatic interactions. Upon exposure to second near‐infrared light, photothermal heat is generated by mARC to induce cytotoxicity to the cancer cell. Meanwhile, quercetin is released to undermine the thermos‐resistance of cancer cells, and IL‐8 siRNA on the mARC surface escapes from endosomes for IL‐8 gene silencing, resulting in highly enhanced PTT. A small animal model is used to study and evaluate the efficacy and toxicity of mARC in vivo. The proposed therapeutic strategy sheds new light on cancer therapy and provides valuable references for future clinical translation.