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 Cu_(2-x)Se nanoparticles(NPs)and DSF(DSF/Cu_(2-x)Se@PCM).Once triggered by second near-infrared(NIR-II)light irradiation,the reactor swiftly releases Cu_(2-x)Se NPs and DSF,enabling catalytic reactions that lead to the rapid and massive production of Cu_(2-x)Se-ET complexes,thereby achieving in situ chemotherapy.The mechanism of the burst reaction is due to the unique properties of ultrasmall Cu_(2-x)Se 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 Cu_(2-x)Se,forming Cu_(2-x)Se-ET complexes without the need for copper ion release.Additionally,Cu_(2-x)Se-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 Cu_(2-x)Se,presents a promising approach for the development of innovative nanoplatforms in the field of precise tumor chemotherapy.