developed pH‐responsive lipid nanoparticles (NL/PLDs) loaded with PCSK9 shRNA, lonidamine (LND), and low‐dose doxorubicin (DOX), which effectively alleviated the tumor immune‐suppressive microenvironment (TIME) and enhanced CD8+ T cell‐mediated anticancer immunity. The gene discussed is CD8A; the disease is neoplasm.