"Zombie" Macrophages for Targeted Drug Delivery to Treat Acute Pneumonia

A cell-based drug delivery systemhas emerged as a promisingdrugdelivery platform. Due to their innate inflammatory tropism, naturaland engineered macrophages have exhibited targeted accumulation ininflammatory tissues, which has allowed targeted delivery of medicinefor the treatment of a variety of inflammatory diseases. Nevertheless,live macrophages may take up the medicine and metabolize it duringpreparation, storage, and in vivo delivery, sometimes causing unsatisfactorytherapeutic efficacy. In addition, live macrophage-based drug deliverysystems are usually freshly prepared and injected, due to the poorstability that does not allow storage. "Off-the-shelf"products would be indeed conducive to the timely therapy of acutediseases. Herein, a cryo-shocked macrophage-based drug delivery systemwas developed via supramolecular conjugation of cyclodextrin (CD)-modified"zombie" macrophages and adamantane (ADA)-functionalizednanomedicine. "Zombie" macrophages exhibited a muchbetter storage stability over time than their counterpart live macrophagedrug carriers and maintained cell morphology, membrane integrity,and biological functions. In an acute pneumonia mouse model, "zombie"macrophages carried quercetin-loaded nanomedicine, hand-in-hand, tothe inflammatory lung tissues and effectively alleviated the inflammationin mice.