A cell-based drug delivery system
has emerged as a promising
drug
delivery platform. Due to their innate inflammatory tropism, natural
and engineered macrophages have exhibited targeted accumulation in
inflammatory tissues, which has allowed targeted delivery of medicine
for the treatment of a variety of inflammatory diseases. Nevertheless,
live macrophages may take up the medicine and metabolize it during
preparation, storage, and in vivo delivery, sometimes causing unsatisfactory
therapeutic efficacy. In addition, live macrophage-based drug delivery
systems are usually freshly prepared and injected, due to the poor
stability that does not allow storage. “Off-the-shelf”
products would be indeed conducive to the timely therapy of acute
diseases. Herein, a cryo-shocked macrophage-based drug delivery system
was developed via supramolecular conjugation of cyclodextrin (CD)-modified
“zombie” macrophages and adamantane (ADA)-functionalized
nanomedicine. “Zombie” macrophages exhibited a much
better storage stability over time than their counterpart live macrophage
drug 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, to
the inflammatory lung tissues and effectively alleviated the inflammation
in mice.