Crossing lung barriers: inhalable biomaterials for lung cancer from design to application.

Lung cancer remains the leading cause of cancer death worldwide. Systemic drug delivery often results in low lung accumulation and high toxicity. Inhalable biomaterials offer a promising alternative by delivering therapeutics directly to lung lesions, enabling high local concentrations and minimal systemic exposure. This review systematically summarizes recent advances in inhalable bio-nanomaterials for lung cancer therapy. We first analyze key pulmonary barriers-mucus, surfactant, alveolar-capillary barrier, and macrophage clearance-and then outline material design strategies based on particle size, morphology, and surface engineering. The review highlights progress in inhaled immunomodulation (tumor vaccines and immune checkpoint modulation) and combination therapies (chemotherapy, physical fields, ferroptosis, and radiotherapy). Finally, we discuss device compatibility and clinical translation challenges. This review provides a practical reference for developing inhalable biomaterials toward precision lung cancer treatment.