This study aims to investigate the mechanism of action of Tumor-Targeting Peptide 1-modified cancer stem cell-derived extracellular vesicles encapsulating transformable specific-responsive peptide (TMTP1-TSRP-EVs) in reshaping the TME, preventing bone metastasis of PI3K-mutant NSCLC, and reversing primary immune checkpoint resistance. The gene discussed is PIK3CA; the disease is non-small cell lung carcinoma.