Journal
ADVANCED SCIENCE
Volume 8, Issue 15, Pages -Publisher
WILEY
DOI: 10.1002/advs.202100787
Keywords
Biomimetic; macrophages; membrane fusion; miRNAs; monocytes; myocardial ischemia-reperfusion injury; platelets
Categories
Funding
- National Natural Science Foundation of China [82070281, 81801374]
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A platelet-like fusogenic liposome (PLPs) was developed to deliver mesoporous silica nanospheres loaded with anti-inflammatory agent miR-21 to the inflammatory monocytes in MI/R induced mice, achieving reparative reprogramming of inflamed macrophages and preserving cardiac function effectively. This nano-platform shows promise as a minimally invasive and biologically safe approach for immunotherapy.
Inflammatory modulations focusing on macrophage phenotype are promising candidates to promote better cardiac healing post myocardial ischemia-reperfusion (MI/R) injury. However, the peak of monocyte/macrophage recruitment is later than the time when enhanced permeability and retention effect disappears, which greatly increases the difficulty of reprogramming macrophages through systemic administration. Meanwhile, the inability of nanomaterials to release their contents to specific intracellular locations through reasonable cellular internalization pathways is another obstacle to achieving macrophage reprogramming. Here, inspired by the increase in circulating platelet-monocyte aggregates in patients ' post-MI/R and the high efficiency of fusogenic liposomes to deliver contents to the cytoplasm of target cells, a platelet-like fusogenic liposome (PLPs) is constructed. Under the coating of PLPs, mesoporous silica nanospheres with a payload of miR-21, an anti-inflammatory agent, can be specifically delivered to inflammatory monocytes in the blood circulation of MI/R induced mice. Then it directly enters the cytoplasm of monocytes through membrane fusion, thereby realizing the reparative reprogramming of the inflamed macrophages derived from it. In vivo administration of the resulting formula can effectively preserve the cardiac function of mice undergone MI/R. Minimal invasiveness and biological safety make this nano-platform a promising approach of immunotherapy.
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