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"Zombie" Macrophages for Targeted Drug Delivery to Treat Acute Pneumonia
Xun Xu1, Cheryl H T Kwong1, Junyan Li1
1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China.
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.
Insights
Researchers developed "zombie" macrophages for stable, off-the-shelf drug delivery. These engineered cells effectively target inflammatory lung tissue, improving therapeutic outcomes for diseases like pneumonia.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Immunology
Background:
- Cell-based drug delivery systems, particularly using macrophages, show promise for targeting inflammatory diseases.
- Live macrophages face limitations including drug metabolism and poor storage stability, hindering therapeutic efficacy and timely treatment.
- The need for stable, readily available drug delivery platforms is critical for managing acute inflammatory conditions.
Purpose of the Study:
- To develop a stable, cryo-shocked macrophage-based drug delivery system for enhanced therapeutic applications.
- To investigate the stability and drug-carrying capabilities of "zombie" macrophages compared to live macrophages.
- To evaluate the efficacy of this novel system in an acute pneumonia mouse model.
Main Methods:
- Development of "zombie" macrophages through cryo-shocking and supramolecular conjugation with cyclodextrin (CD)-modified surfaces.
- Functionalization of nanomedicine with adamantane (ADA) for conjugation with "zombie" macrophages.
- Assessment of "zombie" macrophage stability, morphology, membrane integrity, and biological functions.
- In vivo evaluation using an acute pneumonia mouse model with quercetin-loaded nanomedicine carried by "zombie" macrophages.
Main Results:
- "Zombie" macrophages demonstrated significantly improved storage stability over time compared to live macrophages.
- Cell morphology, membrane integrity, and essential biological functions were preserved in "zombie" macrophages.
- In the acute pneumonia model, "zombie" macrophages successfully delivered quercetin-loaded nanomedicine to inflamed lung tissues.
- Effective alleviation of inflammation was observed in mice treated with the "zombie" macrophage drug delivery system.
Conclusions:
- Cryo-shocked "zombie" macrophages offer a stable and effective platform for nanomedicine drug delivery.
- This novel system overcomes the limitations of live macrophage carriers, enabling "off-the-shelf" applications for acute diseases.
- The "zombie" macrophage system shows significant potential for targeted therapy of inflammatory lung diseases.
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