Lung cancer is the second most prevalent and the deadliest among all cancer types.Chemotherapy is recommended for lung cancers to control tumor growth and to prolong patient survival.Systemic chemotherapy typically has very limited efficacy as well as severe systemic adverse effects,which are often attributed to the distribution of anticancer drugs to non-targeted sites.In contrast,inhalation routes permit the delivery of drugs directly to the lungs providing high local concentrations that may enhance the antitumor effect while alleviating systemic adverse effects.Preliminary studies in animals and humans have suggested that most inhaled chemotherapies are tolerable with manageable pulmonary adverse effects,including cough and bronchospasm.Promoting the deposition of anticancer drugs in tumorous cells and minimizing access to healthy lung cells can further augment the efficacy and reduce the risk of local toxicities caused by inhaled chemotherapy.Sustained release and tumor localization characteristics make nanoparticle formulations a promising candidate for the inhaled delivery of chemotherapeutic agents against lung cancers.However,the physiology of respiratory tracts and lung clearance mechanisms present key barriers for the effective deposition and retention of inhaled nanoparticle formulations in the lungs.Recent research has focused on the development of novel formulations to maximize lung deposition and to minimize pulmonary clearance of inhaled nanoparticles.This article systematically reviews the challenges and opportunities for the pulmonary delivery of nanoparticle formulations for the treatment of lung cancers.