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 CuSe nanoparticles (NPs) and DSF (DSF/CuSe@PCM). Once triggered by second near-infrared (NIR-II) light irradiation, the reactor swiftly releases CuSe NPs and DSF, enabling catalytic reactions that lead to the rapid and massive production of CuSe-ET complexes, thereby achieving chemotherapy. The mechanism of the burst reaction is due to the unique properties of ultrasmall CuSe 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 CuSe, forming CuSe-ET complexes without the need for copper ion release. Additionally, CuSe-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 explosive generation of tumor-suppressive substances mediated by the size and valence of CuSe, presents a promising approach for the development of innovative nanoplatforms in the field of precise tumor chemotherapy.