NIR-II light triggered burst-release cascade nanoreactor for precise cancer chemotherapy

The current strategy of co-delivering copper ions and disulfiram (DSF) to generate cytotoxic CuET faces limitations in achieving rapid and substantial CuET production, specifically in tumor lesions. To overcome this challenge, we introduce a novel burst-release cascade reactor composed of phase change materials (PCMs) encapsulating ultrasmall Cu2-xSe nanoparticles (NPs) and DSF (DSF/Cu2-xSe@PCM). Once triggered by second near-infrared (NIR-II) light irradiation, the reactor swiftly releases Cu2-xSe NPs and DSF, enabling catalytic reactions that lead to the rapid and massive production of Cu2-xSe-ET complexes, thereby achieving in situ chemotherapy. The mechanism of the burst reaction is due to the unique properties of ultrasmall Cu2-xSe NPs, including their small size, multiple defects, and high surface activity. These characteristics allow DSF to be directly reduced and chelated on the surface defect sites of Cu2-xSe, forming Cu2-xSe-ET complexes without the need for copper ion release. Additionally, Cu2-xSe-ET has demonstrated a similar (to CuET) anti-tumor activity through increased autophagy, but with even greater potency due to its unique two-dimensional-like structure. The light-triggered cascade of interlocking reactions, coupled with in situ explosive generation of tumor-suppressive substances mediated by the size and valence of Cu2-xSe, presents a promising approach for the development of innovative nanoplatforms in the field of precise tumor chemotherapy.