Responsive nanoheterojunctions for built‐in electric field‐promoted cascade tumor targeting and cuproptosis‐based therapy

Abstract It is desirable to achieve a high‐efficiency tumor elimination along with treating mildness, minimized side‐effects and operational convenience. Herein, engineered nanoheterojunctions of BCIPTH have been synthesized as responsive biomaterials for cascade targeting of tumor cells and mitochondria, and reactive oxygen species‐mediated apoptosis and Cu‐promoted cuproptosis as paralleled programed cell death. Furthermore, drug‐device‐field integration (DDFI), which derived from drug‐device combination (DDC), was employed by incorporating the heterojunctions, medical laser, intrinsic microelectric field and external physical fields for photo‐triggered tumor cell elimination in vitro and lesion eradication in vivo. A prominent tumor inhibition of 85.4% was found in the MCF‐7‐exnografted nude mice treatment, and a proposed anti‐tumor mechanism of mitochondrial dysfunctions and bio‐informatics‐concluded signaling pathways have been explored. This study consequently brought an interesting example of advanced tumor treatment paradigm, and will be unprecedentedly advancing the evolution of DDC and shedding promising inspirations to future studies on the treatments of related diseases by DDFI.