Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

Cuproptosis is an emerging regulated cell death that depends on the intracellular copper ion and mitochondrial respiration, showing great potential in cancer treatment. However, increasing specific accumulation of ions mitochondria while simultaneously enhancing respiration are highly needed still a major challenge to promote cuproptosis. Herein, lactate dehydrogenase (LDH) inhibitor galloflavin (GF) self-assembles with ionophore elesclomol (ES) through ion-driven cooperative coordination form GF/CuES nanoparticles, synergistically targeting anaerobic glycolysis boost cuproptosis-immunotherapy. After cellular internalization, nanoparticles responsively dissociate release Cu²⁺ ES, co-transporting into collaboratively trigger cuproptosis, which subsequently evokes immunogenic (ICD). Notably, liberated GF leads effective LDH suppression, not only further amplifies cuproptosis via disrupting but also reduces production, thus alleviating immunosuppressive tumor microenvironment augmenting anti-tumor immunity driven by ICD. Thus, exhibit strong antitumor effects cooperatively glycolysis, immunotherapy, offering unique opportunity enhance treatment strategies.

Language: Английский