Nanoformulations: Reforming treatment for non-small cell lung cancer metastasis.

Non-small cell lung cancer (NSCLC) is frequently diagnosed at an advanced stage, with 20 % of cases presenting as localized disease, 25 % with regional metastasis, and 55 % with distant metastasis, contributing significantly to increased morbidity and mortality rates. Current treatments, including chemotherapy, immunotherapy, radiotherapy and targeted therapy, have shown therapeutic efficacy but are limited by issues such as lack of specificity, cytotoxicity, and therapeutic resistance. Nanoparticles (NPs) offer promising solutions to these challenges by enhancing drug penetration and retention, improving biocompatibility and stability, and achieving greater precision in targeting cancer cells. This review provides insights into various types of NPs utilized in anti-metastatic drug delivery, emphasizing their ability to enhance the efficacy of existing chemotherapeutics for the prophylaxis of metastatic NSCLC. The usage of NPs as carriers of synthetic and natural compounds aimed at inhibiting cancer cell migration and invasion have also been reviewed. Special attention has been given to biomimetic nanomaterials including extracellular vesicles and engineered exosomes, that are capable of targeting molecular pathways such as EMT, p53 and PI3K/Akt to treat metastatic NSCLC. Additionally, emphasis has been given to clinical trials of these nanoformulations and their efficacy. Although therapeutic outcomes have demonstrated certain improvements, challenges related to toxicity persist, highlighting the need for further optimization of these formulations to enhance safety and efficacy. Finally, we discuss the current limitations and future perspectives for integrating NPs into clinical settings as novel therapeutic agents for lung cancer metastasis.