Inducing pyroptosis and reprogramming macrophage via zeolitic imidazolate framework encapsulated-fullerene for two-pronged tumor immunotherapy.

ABSTRACT: Immunogenic antigen downregulation combined with an immunosuppressive tumor microenvironment (TME) remain major barriers to effective treatment of "cold" tumors. Here, we report a dual-functional nanotherapy that integrates C₇₀ fullerene with hyaluronic acid (HA)-modified zeolitic imidazolate framework-8 (ZIF-8) to enhance tumor immunogenicity and reprogram the TME. The resulting HA-C₇₀@ZIF-8 nanocomposites exploit HA-mediated CD44 targeting to promote selective tumor uptake and retention. Once internalized, acidic lysosomal conditions trigger Zn²⁺ release from ZIF-8, causing ion overload, caspase-1 activation, gasdermin D cleavage, and pyroptotic tumor cell death accompanied by the release of damage-associated molecular patterns (DAMPs). Concurrently, enca

SUBMITTER: Sun Z 

PROVIDER: S-EPMC12615320 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature