Targeted therapies of inflammatory diseases with intracellularly gelated macrophages in mice and rats.
Cheng GaoQingfu WangYuanfu DingCheryl H T KwongJinwei LiuBeibei XieJianwen WeiSimon M Y LeeGreta S P MokRuibing WangPublished in: Nature communications (2024)
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.
Keyphrases
- oxidative stress
- induced apoptosis
- rheumatoid arthritis
- anti inflammatory
- diabetic rats
- high fat diet induced
- respiratory failure
- liver failure
- air pollution
- drug induced
- particulate matter
- room temperature
- high dose
- high resolution
- type diabetes
- fatty acid
- mesenchymal stem cells
- small molecule
- metabolic syndrome
- insulin resistance
- protein protein
- low dose
- endoplasmic reticulum stress
- cell therapy
- cell death
- extracorporeal membrane oxygenation
- drug delivery
- aortic dissection
- ionic liquid
- pi k akt