Self-assembled S-Cu(I)-S sites were spatially isolated onto a two-dimensional Ti3C2 surface to produce a structurally well-defined and highly functional single-site copper(I) nanomodulator CuNTD, which can induce severe immunogenic cell death through multiple regulatory pathways of synergistic cascade photothermal-amplified ROS storms, cuproptosis and ferroptosis for cancer immunotherapy.
Abstract:
Nanozyme-based immunogenic cell death (ICD) inducers that effectively induce a strong immune response via enzyme-like process have attracted great attention, but how to ensure controllable active sites and maximize site utilization remains a problem. Here, we report a structurally well-defined and highly functional single-site copper(I) nanomodulators termed CuNTD, constructed by precisely anchoring atomically dispersed self-assembly S-Cu(I)-S sites onto a two-dimensional Ti3C2 surface. Leveraging Cu+ with a higher catalytic efficiency than Cu2+, CuNTD generates reactive oxygen species (ROS) storms through photothermal-enhanced cascade catalysis, further inducing mitochondrial dysfunction, ferroptosis and cuproptosis. Multifunctional CuNTD triggers strong ICD through cascade-regulatory pathways of photothermal-amplified ROS storms, cuproptosis and ferroptosis, effectively promoting dendritic cell maturation while reducing monotherapies side effects and resistance. In vivo, CuNTD combined with FDA-approved immunoadjuvants significantly prolong the survival of mice. With its demonstrated biosafety and high efficiency as an ICD inducer, this study provides a promising framework for advancing augmented tumor immunotherapy with significant clinical potential.
Author list:
Yuanyuan Zhang, Shengnan Ya, Jingnan Huang, Yangyang Ju, Xueyang Fang, Xinteng Ouyang, Qingdong Zeng, Xinyao Zhou, Xiyun Yan, Guohui Nie*, Kelong Fan*, Bin Zhang*
How to cite:
Y. Zhang, S. Ya, J. Huang, Y. Ju, X. Fang, X. Ouyang, Q. Zeng, X. Zhou, X. Yan, G. Nie, K. Fan, B. Zhang, Exploration 2025, 20240275.
https://doi.org/10.1002/EXP.20240275