Inhaled NIR‐II Nanocatalysts for Real‐Time Monitoring and Immunomodulatory Therapy of Acute Lung Injury

Abstract Acute lung injury (ALI) poses a significant and escalating medical challenge, where precise diagnosis and timely intervention hold utmost importance in halting its deterioration. Nevertheless, persistent obstacles arise from the lack of agents proficient in both real‐time diagnosis and efficient mitigation of ALI. Here, a biocatalytic and second near‐infrared (NIR‐II) fluorescence‐illuminating nanoplatform is designed to simultaneously facilitate real‐time monitoring and robust inflammation alleviation in ALI. The study first develops a new aggregation‐induced emission luminogen with trifluoromethyl substitutions, which simultaneously increase NIR‐II emission wavelength and fluorescence brightness. The molecular probe is further integrated into biocatalytic hollow ceria nanostructures, and cloaked with pre‐activated macrophage membranes for targeted inflammation intervention. Upon inhalation administration in ALI mice, the theranostic nanoagents leverage the bright NIR‐II emission and active inflammation‐tropic properties for in vivo sensitive NIR‐II imaging of ALI, which also facilitates real‐time tracking of the nanoagents’ distribution and dynamic fate within pneumonia milieu. Concurrently, the catalytic prowess of the nanoplatforms efficaciously scavenges excess reactive oxygen species, dampens proinflammatory cytokines, and promotes macrophage repolarization, substantially alleviating acute lung damage. The multifaceted nanoplatform integrates NIR‐II bioimaging with nanocatalysis‐mediated immunoregulation, offering a versatile and promising approach for addressing the intricate challenges posed by acute inflammation diseases.