Supramolecular erythrocytes-hitchhiking drug delivery system for specific therapy of acute pneumonia

Acute pneumonia is an inflammatory syndrome often associated with severe multi-organ dysfunction and high mortality. The therapeutic efficacy of current anti-inflammatory medicines is greatly limited due to the short systemic circulation and poor specificity in the lungs. New drug delivery systems (DDS) are urgently needed to efficiently transport anti-inflammatory drugs to the lungs. Here, we report an inflammation-responsive supramolecular erythrocytes-hitchhiking DDS to extend systemic circulation of the nanomedicine via hitchhiking red blood cells (RBCs) and specifically “drop off” the payloads in the inflammatory lungs. β-cyclodextrin (β-CD) modified RBCs and ferrocene (Fc) modified liposomes (NP) were prepared and co-incubated to attach NP to RBCs via β-CD/Fc host-guest interactions. RBCs extended the systemic circulation of the attached NP, meanwhile, the NP may get detached from RBCs due to the high ROS level in the inflammatory lungs. In acute pneumonia mice, this strategy delivered curcumin specifically to the lungs and effectively alleviated the inflammatory syndrome. [Display omitted] •Liposomes were attached to red blood cells (RBCs) via host-guest interactions.•The supramolecular conjugates specifically “drop off” the liposomes in response to the inflammatory microenvironment.•This stragety effectively alleviated lung edema, down-regulated inflammatory cytokines, and repolarized macrophage.•This precisely controlled cell-hitchhiking strategy provides a general platform for site-specific drug delivery.