Right Cu2−xS@MnS Core–Shell Nanoparticles as a Photo/H2O2‐Responsive Platform for Effective Cancer Theranostics

Abstract Stimuli‐responsive nanomedicines have become a recent research focus as a candidate for cancer treatment because of their effectiveness, sensibility, and minimal invasiveness. In this work, a novel nanosystem is developed based on Cu 2− x S@MnS core–shell nanoparticles (CSNPs) in which the Cu 2− x S core serves as a photosensitizer to generate hyperthermia and reactive oxygen species (ROS), and the MnS shell is used in H 2 O 2 ‐responsive O 2 production. Cu 2 −x S@MnS CSNPs with an independent core and shell ratio are synthesized by a controllable hot‐injection method, resulting in an optimal photothermal (PT) effect with a PT conversion efficiency of up to 47.9%. An enhanced photodynamic (PD) effect also occurs in an H 2 O 2 environment. More significantly, in vivo experiments demonstrate that Cu 2 −x S@MnS CSNPs can mediate tumor shrinkage in both HeLa tumor cell line‐derived xenograft (CDX) and head and neck squamous cell carcinoma (HNSCC) patient‐derived xenograft (PDX) models, with the capability of being used as a T1‐enhanced magnetic resonance (MR) contrast agent. These results suggest the great potential of as‐prepared Cu 2 −x S@MnS CSNPs as photo/H 2 O 2 ‐responsive therapeutic‐agents against tumors, even in a complicated and heterogeneous environment, thus promoting the clinical translation of nanomedicine.