Inhalable Herbal Nano-Liposomes Co-Delivering Astragaloside IV and Polyphyllin VII Reprogram Immunosuppressive Microenvironment To Overcome Anti-PD-1 Resistance in NSCLC.

ABSTRACT: Non-small cell lung cancer (NSCLC) frequently develops acquired resistance to immune checkpoint inhibitors (ICIs), necessitating innovative strategies to remodel the immunosuppressive tumor microenvironment (TME). This study engineered an inhalable pH-responsive nano-liposome co-delivering Astragaloside IV (AS-IV) and Polyphyllin VII (Pol VII) (AS-IV/Pol VII-Lipo) to overcome anti-PD-1 resistance via spatiotemporal-controlled dual-drug delivery. AS-IV/Pol VII-Lipo (1:1 mass ratio) exhibited optimal physicochemical properties: high drug loading and pH-triggered release. Nebulized inhalation achieved 3.4-fold higher lung accumulation than oral administration. Suppressed orthotopic LLC-Luc tumor growth by 54% and reduced exhausted CD8⁺ T cells while increasing cytotoxic CD8⁺Granzyme B⁺ T cell

SUBMITTER: Liu Y 

PROVIDER: S-EPMC12604339 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature