Macrophage-Targeted Nanomedicines for ARDS/ALI: Promise and Potential

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are characterized by progressive lung impairment typically triggered by inflammatory processes. The mortality toll for ARDS/ALI yet remains high because of the poor prognosis, lack of disease-specific inflammation management therapies, and prolonged hospitalizations. The urgency for the development of new effective therapeutic strategies has become acutely evident for patients with coronavirus disease 2019 (COVID-19) who are highly susceptible to ARDS/ALI. We propose that the lack of target specificity in ARDS/ALI of current treatments is one of the reasons for poor patient outcomes. Unlike traditional therapeutics, nanomedicine offers precise drug targeting to inflamed tissues, the capacity to surmount pulmonary barriers, enhanced interactions with lung epithelium, and the potential to reduce off-target and systemic adverse effects. In this article, we focus on the key cellular drivers of inflammation in ARDS/ALI: macrophages. We propose that as macrophages are involved in the etiology of ARDS/ALI and regulate inflammatory cascades, they are a promising target for new therapeutic development. In this review, we offer a survey of multiple nanomedicines that are currently being investigated with promising macrophage targeting potential and strategies for pulmonary delivery. Specifically, we will focus on nanomedicines that have shown engagement with proinflammatory macrophage targets and have the potential to reduce inflammation and reverse tissue damage in ARDS/ALI. GRAPHICAL ABSTRACT: [Image: see text]