Inhalable nanoparticles with enhanced cuproptosis and cGAS-STING activation for synergistic lung metastasis immunotherapy.

ABSTRACT: Due to the insufficient Cu⁺ accumulation, Cu⁺ efflux mechanism, and highly immunosuppressive tumor microenvironment (TME) in lung metastasis, the cuproptosis efficacy is limited. Herein, an inhalable nanodevice (CLDCu) is constructed to successfully overcome the drawbacks of cuproptosis. CLDCu consists of a Cu²⁺-chitosan shell and low molecular weight heparin-tocopherol succinate (LMWH-TOS, LT) core with disulfiram (DSF) loading. The prepared CLDCu can be inhaled and accumulate in large amounts in lung lesions (63.6%) with 56.5 times higher than intravenous injection. Within tumor cells, the mild acidity triggers the co-release of DSF and Cu²⁺, thus generating bis(diethyldithiocarbamate)-copper (CuET) to block Cu⁺ efflux protein ATP7B

SUBMITTER: Yan C 

PROVIDER: S-EPMC11365430 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature