Preclinical study reveals inhaled surfactant nanoparticles suppress tumor growth and reprogram macrophages in murine lung cancer, suggesting a viable local inhalation strategy.
Key Points
To develop pemetrexed-functionalized, pulmonary surfactant-based nanoparticles loaded with paclitaxel for inhalation therapy that co-targets lung cancer cells and tumor-associated macrophages.
Synthesized pemetrexed-modified pulmonary surfactant nanoparticles encapsulating paclitaxel (PEM-PSNP@PTX) to integrate into the endogenous alveolar surfactant layer.
Characterized aerosol stability, nanoparticle size, cellular uptake, and selective cytotoxicity in folate receptor-positive versus folate receptor-negative cells.
Evaluated in vivo pulmonary retention, systemic toxicity, antitumor efficacy, survival outcomes, and immune cytokine changes in bronchoalveolar lavage fluid using a mouse lung cancer model.
PEM-PSNP@PTX exhibited a mean particle size of 135.3 nm, 17.6% drug loading, robust nebulization stability, and lung retention for up to 48 hours with minimal systemic distribution.
Inhaled PEM-PSNP@PTX significantly suppressed tumor progression and extended survival in tumor-bearing mice with no observed systemic toxicity compared to free paclitaxel and PLGA controls.
Treatment reconditioned the tumor microenvironment by elevating CD86, IL-12, and TNF-α while reducing CD206, IL-10, and TGF-β, confirming macrophage repolarization from an M2 to an M1 phenotype.