Inhalable Chemotactic Liposome for Targeted Modulation of Pulmonary Pre‐Metastatic Niche

Abstract Inhalation offers a non‐invasive method to administer drugs to lungs, but achieving selective delivery to pulmonary lesions while sparing normal lung tissues remains challenging. Here, the development of an inhalable chemotactic liposome designed for targeted modulation of pulmonary pre‐metastatic niche (PMN) is reported. The inhaled liposome can migrate along chemokine gradients, preferentially accumulating in chemokine‐secreting PMNs within the lung. Upon localized drug release, the liposome mitigates fibrosis, and disrupts PMN evolution, thereby attenuating the pro‐metastatic role of PMN as a hospitable “soil” for residual tumor cell “seeding” post‐surgery. This approach further complements a sprayable hydrogel developed for immediate post‐surgical application within the tumor resection cavity. While this hydrogel alone reduces the metastatic potential of postoperative tumor residues, it proves insufficient in halting the spread to lungs. However, the integration of the inhalable liposome and sprayable hydrogel into a dual‐pronged strategy presents a patient‐friendly method that simultaneously targets both the pro‐metastatic PMN “soil” and metastatic tumor “seeds”, resulting in significant inhibition of postoperative lung metastasis.