Figure 1.

Schematic illustration for the synthesis of tPF@PCM and the synergistic mechanism for cancer therapy. Briefly, PF@PCM was first synthesized via nanoprecipitation and resolidification methods and then coupled with tLyP-1. The obtained tPF@PCM was next injected to 786-O tumor-bearing mice via the tail vein. At a local temperature of 45 °C by laser irradiation, Fe₃O₄ NPs were released from tPF@PCM and triggered the generation of ROS efficiently, resulting in increased unfolded or misfolded proteins in the ER lumen. The DUB inhibitor PR-619 suppressed the degradation of these damaged proteins, exacerbating ER stress, and finally leading to apoptosis of cancer cells. ① NIR-activated solid-to-liquid phase transition of tPF@PCM and release of Fe₃O₄ NPs and PR-619. ② Production of ROS via enhanced Fenton reaction by moderate heat of 45 °C. ③ Ubiquitination of unfolded and misfolded proteins. ④ Recognition of ubiquitinated proteins by the proteasome. ⑤ Deubiquitination of ubiquitinated proteins mediated by deubiquitinase. ⑥ Degradation of damaged proteins by the proteasome. ⑦ Recycling of ubiquitins after deubiquitination.