Therapeutic Efficacy Of Tmtp1modified Evs In Overcoming Bone Metastasis And Immune Resistance In Pik3ca Mutant Nsclc Liwen Liu Tanghesi Wuyun Xin Sun Yu Zhang Geqi Cha Ling Zhao by Liwen Liu & Tanghesi Wuyun & Xin Sun & Yu Zhang & Geqi Cha & Ling Zhao 101038/S4141902507685Y instant download after payment.

Non-small cell lung cancer (NSCLC) with PIK3CA mutations demonstrates significant challenges in treatment due to enhanced bonemetastasis and immune checkpoint resistance. This study investigates the efficacy of tumor-targeting peptide 1-modified cancerstem cell-derived extracellular vesicles (TMTP1-TSRP-EVs) in reshaping the tumor microenvironment and reversing immunecheckpoint resistance in NSCLC. By integrating TMTP1-TSRP into EVs, we aim to specifically deliver therapeutic agents to NSCLCcells, focusing on inhibiting the PI3K/Akt/mTOR pathway, a crucial driver of oncogenic activity and immune evasion in PIK3CA1234567890();,:mutated cells. Our comprehensive in vitro and in vivo analyses show that TMTP1-TSRP-EVs significantly inhibit tumor growth,reduce PD-L1 expression, and enhance CD8+ T cell infiltration, effectively reversing the immune-suppressive microenvironment.Moreover, the in vivo models confirm that our approach not only suppresses bone metastases but also overcomes primaryresistance to immune checkpoint inhibitors by modulating the expression of key immunological markers. These findings suggestthat targeted delivery of TMTP1-TSRP-EVs could provide a novel therapeutic strategy for treating PIK3CA-mutant NSCLC, offeringsignificant improvements over traditional therapies by directly targeting the molecular pathogenesis of tumor resistance andmetastasis.Cell Death and Disease (2025) 16:367 ;