Conclusion
The dual-targeting liposomal codelivery system offers a promising strategy for treating the advanced EGFRT790M NSCLC patients with BMs.
Methods
Tumor-associated macrophages (TAM) is a promising drug target for inhibiting tumor growth, overcoming drug resistance, and anti-metastasis. TAM also plays an essential role in regulating tumor microenvironment. We developed a dual-targeting liposomal system with modification of anti-PD-L1 nanobody and transferrin receptor (TfR)-binding peptide T12 for codelivery of simvastatin/gefitinib to treat BMs of NSCLC.
Results
The dual-targeting liposomes could efficiently penetrate the blood-brain barrier (BBB) and enter the BMs, acting on TAM repolarization and reversal of EGFRT790M-associated drug resistance. The treatment mechanisms were related to the elevating ROS and the suppression of the EGFR/Akt/Erk signaling pathway.