“Zombie” Macrophages for Targeted Drug Delivery to Treat Acute Pneumonia

Abstract

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.

Hyperosmotic cold shock mouse melanoma cells encapsulated with doxorubicin for targeted treatment of melanoma

“…The preparation process was based on previously reported methods ( 19 , 23 , 25 ) with minor modifications. Initially, B16F10 cells were harvested, centrifuged at 1000 rpm for 5 min, and resuspended in 40% glucose.…”

“…However, immunotherapy has limitations, including partial patient resistance to treatment, few effective biomarkers to predict treatment response, and the precise selection of patients suitable for immunotherapy (17,18). Cells have been considered promising drug delivery systems because of their high biocompatibility and low immunogenicity, allowing them to avoid removal by the reticuloendothelial system (19). Additionally, cells can communicate with the cells of tissues or organs in the body, allowing them to accumulate in specific tissues or organs to deliver targeted drugs (19)(20)(21).…”

“…Cells have been considered promising drug delivery systems because of their high biocompatibility and low immunogenicity, allowing them to avoid removal by the reticuloendothelial system (19). Additionally, cells can communicate with the cells of tissues or organs in the body, allowing them to accumulate in specific tissues or organs to deliver targeted drugs (19)(20)(21). However, clinical treatments that use living cells have reported challenges, such as the rapid loss of cellular activity outside the body and the low drug capacity of many living cells.…”