Imaging Identifies Superior Inflammation Targeting of M1 Macrophages for Cryo‐Shocked Cell Pulmonary Drug Delivery to Treat Acute Lung Injury

Abstract In the realm of combating acute lung injury (ALI) induced by a myriad of triggers including sepsis, pneumonia, aspiration, trauma, and pancreatitis, macrophages emerge as crucial players. However, traditional treatments such as systemic administration of glucocorticoids come with the baggage of severe side effects, curtailing their utility. Enter an innovative solution: a biomimetic drug delivery system fashioned from cryo‐shocked macrophages, tailored for pulmonary drug delivery. Positron emission tomography (PET) imaging has shed light on the remarkable targeting abilities of live M1 macrophages, showcasing their unparalleled efficacy in homing in on local inflammatory foci when contrasted with naive, M1, and M2 macrophages. Building upon this foundation, liquid nitrogen‐treated (LNT) M1 macrophages are developed, engineered to preserve their inflammation‐targeting prowess while sidestepping the release of pro‐inflammatory cytokines. This breakthrough allows for the delivery of glucocorticoids directly to inflamed lung tissues, efficiently quelling inflammation and mitigating pulmonary edema while drastically reducing systemic drug exposure. Inspired by the effectiveness of live M1 macrophages, the potential of glucocorticoid‐loaded LNT M1 macrophages are harnessed, utilizing them as a stealthy “Trojan horse” in the battle against pneumonia‐induced ALI. This innovative approach holds promise as a safe and potent treatment avenue for acute lung injury.