RCMI scientists have developed a new lung cancer treatment using tiny natural packages called "exosomes" from natural killer (NK) immune cells. They loaded these exosomes with two therapeutic microRNAs designed to turn off specific cancer-promoting genes: a) one that helps cancer cells hide from the immune system and b) another that drives tumor growth. The researchers tested this treatment alone and combined with carboplatin chemotherapy against non-small-cell lung cancers that had become resistant to existing targeted drugs like Osimertinib. In laboratory tests, the microRNA-loaded exosomes reduced cancer cell survival by 1.2 to 1.6 times compared to empty exosomes. In mouse studies, combining the loaded exosomes with chemotherapy shrank tumors 3.5 to 4 times more effectively than standard treatment alone, while successfully turning down several molecular pathways that help cancer resist treatment. This approach offers a promising new strategy for treating drug-resistant lung cancers by using natural delivery vehicles containing cancer-fighting molecules directly targeted to tumor cells alongside conventional chemotherapy.