Macrophages (MΦs) are functionally plastic and can rapidly adopt different phenotypes based on the stimuli they received from their surroundings. For instance, (MΦs) can differentiate into pro-inflammatory M1-type secreting various pro-inflammatory cytokines, e.g., IL-6, IL-12 and TNF-α. This is an essential defensive mechanism against invading pathogens, but also contributes to tissue destruction. On the other hand, M2-type MΦs have immunosuppressive activity, produces high level of anti-inflammatory cytokine IL-10 and mediates tissue repair. Their unique plasticity and the balance in between different phenotypes maintain the immune homeostasis in the lung under healthy conditions. The role of these two forms of MΦs are also evident in cancer biology. While tissue resident MΦs those who are of M1 type are exerting the immune challenge to the tumor cells, the M2 type from the tumor microenvironment (TME) are supporting the growth and progression of cancer cells.

Nanodevices are thought to be an ideal agent targeting macrophages owing to their intrinsic nanoscale property suitable for phagocytosis. The induction of MΦs polarization has been employed in various studies, where administration of IL-4 could reprogram the endogenous inflammatory macrophages (M1-type) to anti-inflammatory ones (M2-type), and accelerate resolution of inflammation and lung repair in a STAT6-dependent manner in both LPS and Pseudomonas aeruginosa bacterial pathogen-induced ALI (Acute Lung Injury) mouse models.