Targeted therapies of inflammatory diseases with intracellularly gelated macrophages in mice and rats

Cheng Gao, Qingfu Wang, Yuanfu Ding, Cheryl H. T. Kwong, Jinwei Liu, Beibei Xie, Jianwen Wei, Simon M. Y. Lee, Greta S. P. Mok and Ruibing Wang ()
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Cheng Gao: University of Macau
Qingfu Wang: University of Macau
Yuanfu Ding: University of Macau
Cheryl H. T. Kwong: University of Macau
Jinwei Liu: University of Macau
Beibei Xie: University of Macau
Jianwen Wei: University of Macau
Simon M. Y. Lee: University of Macau
Greta S. P. Mok: University of Macau
Ruibing Wang: University of Macau

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Membrane-camouflaged nanomedicines often suffer from reduced efficacy caused by membrane protein disintegration and spatial disorder caused by separation and reassembly of membrane fragments during the coating process. Here we show that intracellularly gelated macrophages (GMs) preserve cell membrane structures, including protein content, integration and fluidity, as well as the membrane lipid order. Consequently, in our testing GMs act as cellular sponges to efficiently neutralize various inflammatory cytokines via receptor-ligand interactions, and serve as immune cell-like carriers to selectively bind inflammatory cells in culture medium, even under a flow condition. In a rat model of collagen-induced arthritis, GMs alleviate the joint injury, and suppress the overall arthritis severity. Upon intravenous injection, GMs efficiently accumulate in the inflammatory lungs of acute pneumonia mice for anti-inflammatory therapy. Conveniently, GMs are amenable to lyophilization and can be stored at ambient temperatures for at least 1 month without loss of integrity and bio-activity. This intracellular gelation technology provides a universal platform for targeted inflammation neutralization treatment.

Date: 2024
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DOI: 10.1038/s41467-023-44662-5

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