Filamentous Phage for Therapeutic Applications in Non-Small Cell Lung Cancer and Brain Metastases: Recent Prospect

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with brain metastases occurring in 24% to 40% of advanced NSCLC patients and a poor prognosis. Traditional treatment methods for brain metastases, such as surgery and radiotherapy, often result in neurocognitive impairment and brain edema. Furthermore, chemotherapy drugs struggle to penetrate the central nervous system. Third-generation EGFR-TKI drugs that can cross the blood-brain barrier have demonstrated efficacy in treating NSCLC patients with brain metastases, but their benefits are limited to those with specific driver genes. Immunotherapy demonstrated potential in the treatment of NSCLC patients with brain metastases, although the adverse events limited its clinical use. Given these limitations, filamentous phages emerge as a promising bio-nanomaterial due to their unique biosafety profile, high solubility, and ability to facilitate targeted delivery, which can potentially minimize systemic toxicity. This review focuses on two core applications of filamentous phages in NSCLC and brain metastasis therapy: (i) phage display-derived targeting peptides and (ii) intact engineered filamentous phages as delivery scaffolds. As delivery systems, filamentous phages can prolong in vivo circulation time, reduce toxicity, and effectively cross the Blood-Brain Barrier (BBB)-evidences include filamentous phage mediating targeted delivery of chemotherapeutics and siRNA to NSCLC cells, and phage-nanomaterial hybrids enhancing tumor accumulation. The review also elaborates on the clinical translation potential of filamentous phages, including personalized therapy via patient-specific peptide screening, and discusses current limitations. Filamentous phage-based nanocarriers are expected to improve the quality of life of NSCLC patients with brain metastases.