Overall, we provided evidence that the activation and cross-talk of EGFR and MET signaling pathways contributed to TMZ resistance in glioma and developed a nanoinhibitor, BIP-MPC-NP, which could simultaneously mitigate EGFR and MET activation by conjugating EBP and MBP on the surface of NHS-PEG8-Mal modified MPC nanoparticles. Here, MET is linked to central nervous system cancer.