Targeted Intracellular Copper Reservoir Enhances Liver Cancer Immunotherapy.

ABSTRACT: Hepatocellular carcinoma (HCC) is commonly classified as a "cold tumor" due to its low immunogenicity and poor response to conventional immunotherapies. Reprogramming the tumor immune microenvironment (TIME) via cuproptosis presents a promising strategy to enhance immunotherapies. Herein, sono-activatable N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN)-encapsulated cancer-targeted nanoparticles (STCNs) designed to modulate the TIME and potentiate immunotherapy through endogenous cuproptosis are reported, termed "endogenous cuproptosis immunopromotion". STCNs are rapidly internalized by HCC via folate-mediated endocytosis, and ultrasound irradiation triggers the release of TPEN. TPEN then chelates Cu²⁺ from superoxide dismutase, initiating a Fenton-like reaction in

SUBMITTER: Xie T 

PROVIDER: S-EPMC12423925 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature