Right Cu_2- S@MnS Core-Shell Nanoparticles as a Photo/H₂O₂-Responsive Platform for Effective Cancer Theranostics

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- S@MnS core-shell nanoparticles (CSNPs) in which the Cu_2- S core serves as a photosensitizer to generate hyperthermia and reactive oxygen species (ROS), and the MnS shell is used in H₂O₂-responsive O₂ production. Cu₂ 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 H₂O₂ environment. More significantly, in vivo experiments demonstrate that Cu₂ 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 Cu₂ S@MnS CSNPs as photo/H₂O₂-responsive therapeutic-agents against tumors, even in a complicated and heterogeneous environment, thus promoting the clinical translation of nanomedicine.