Flower-like Cu9S8 nanocatalysts with highly active sites for synergistic NIR-II photothermal therapy and chemodynamic therapy.

Chemodynamic therapy (CDT) is a promising reactive oxygen species-based therapeutic strategy for tumor therapy. However, the poor reaction kinetics of CDT agents severely restricts its further application. Herein, protamine stabilized flower-like Cu9S8 (PS@Cu9S8) nanocatalysts are fabricated via a one-pot biomineralization strategy for synergistic second near-infrared (NIR-II) photothermal therapy (PTT) and CDT of tumor. The PS@Cu9S8 nanocatalysts possess a high surface area (40.10 m2 g-1), which is higher than those of the previously reported solid and hollow copper sulfide nanoparticles. The high surface area of PS@Cu9S8 nanocatalysts increases the number of active sites during the Fenton-like reaction, thereby accelerating the efficiency of CDT. Meanwhile, the PS@Cu9S8 nanocatalysts show a high extinction coefficient (21.41 L g-1 cm-1) and photothermal conversion efficiency (42.34%), which results in an outstanding PTT efficiency and facilitate ˙OH generation for CDT. Furthermore, RNA-sequencing unveils the whole-genome expression change of 4T1 cells after PS@Cu9S8 nanocatalyst treatment, revealing the apparent changes in ROS, cell cycle, and apoptosis-related pathways. In vivo experiments proved the good therapeutic efficiency and negligible systematic toxicity of PS@Cu9S8 nanocatalysts. This work not only develops a superior multifunctional nanocatalyst for synergistic PTT and CDT of tumor, but also provides a facile approach to construct high-performance agents for cancer therapy.