Hybrid Membrane-Camouflaged Osimertinib-Loaded Hollow Mesoporous Prussian Blue Nanoparticles for Synergistic Photothermal/Targeted Therapy of Non-Small Cell Lung Cancer

Osimertinib (Osi) is a standard treatment for EGFR mutant NSCLC, but its efficacy is limited by poor bioavailability and adverse effects. To address these limitations, we developed a biomimetic nanoplatform, HM/HMPB@Osi, by encapsulating osimertinib within hollow mesoporous Prussian blue (HMPB) and coating them with a hybrid membrane derived from red blood cells and H1975 lung cancer cells. The Prussian blue core provided strong near-infrared absorption and a high photothermal conversion efficiency (η = 38.76%), enabling effective photothermal therapy. In vitro, HM/HMPB@Osi NPs exhibited selective tumor targeting, cellular uptake, and synergistic reactive oxygen species generation under laser irradiation, leading to enhanced cytotoxicity in NSCLC cells. In vivo, it achieved enhanced tumor accumulation, robust photothermal performance, and remarkable antitumor efficacy with minimal organ toxicity. Collectively, this study demonstrates that the HM/HMPB@Osi platform represents a promising photothermal/targeted therapy strategy for overcoming the limitations of osimertinib monotherapy in NSCLC.