Microfluidic fabrication of peptide modified carrier-free self-assembled crizotinib-metal nanodrugs for NIR fluorescence imaging and dual-pathway therapy of non-small cell lung cancer.

Crizotinib, a first-line multi-kinase inhibitor for non-small cell lung cancer (NSCLC), faces clinical limitations including systemic toxicity, drug resistance, and insufficient tumor-selective accumulation. To address these challenges, we engineered a microfluidic-fabricated carrier-free nanodrugs (CRZ-Fe@MP) through coordination-driven self-assembly of crizotinib and Fe2+ ions, integrated with c-Met-targeting peptides (Met-pep1) modified with near-infrared fluorescence day (MPA). The resulting nanodrugs exhibited pH-responsive drug release in the tumor microenvironment (TME), enabling tumor-activated chemotherapy while Fe2+-mediated Fenton reactions generated hydroxyl radicals (•OH) for synergistic chemo-dynamic therapy (CDT) and ferroptosis induction. Real-time fluorescence imaging-guided therapy revealed enhanced tumor-targeting efficiency through dual targeting mechanisms combining passive Enhanced Permeability and Retention Effect (EPR) and active c-Met recognition. In A549 xenograft models, CRZ-Fe@MP achieved high tumor suppression with concurrent imaging capability and minimized systemic toxicity. This platform synergizes chemo-chemo-dynamic actions with high drug loading, overcoming bioavailability limitations while establishing a resistance-evasive therapeutic paradigm for precise NSCLC theranostics.