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

Pan, Yu-Jing; Zhang, Yang; Chen, Biao-Qi; Zhao, Yi; Wang, Jin-Yang; Li, Chang-Yong; Zhang, Da-Gui; Kankala, Ranjith Kumar et al. · Bioact Mater · 2024

basic_science · Level V

Where this comes from

Abstract

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