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The development of smart nanoagents that can respond to a specific stimulus has gained remarkable interest for treating various kinds of diseases, including atherosclerosis. On the other hand, a cell camouflaging strategy has been considered as a pivotal factor to improve the delivery stealthiness, biocompatibility, and biodegradability of nanocarriers, resolving the shortcomings of PEGylation. In this study, reactive oxygen species (ROS)‐responsive 5‐aminolevulinic acid (ALA) prodrug nanostructures (ROSELLA) encapsulating rapamycin (RAP) are blended with nanoerythrocyte membranes to construct red blood cell membrane (RBCM)/RAP@ROSELLA. These nanoagents are designed to be able to escape the biological barriers, accumulate in atherosclerosis lesions, and enhance the release of drugs in the intracellular milieu due to the magnification of hydrogen peroxide (H2O2). In vitro study proves its superior ability to inhibit the proliferation of macrophages and vascular smooth muscle cells. In vivo developmental toxicity further confirms that no significant systematic toxicity is induced by RBCM/RAP@ROSELLA, implying its favorable biocompatibility, which has potential for precise nanomedicine to combat atherosclerosis.

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Recent studies have focused on capillary pruning in various organs and species. However, the way in which large-diameter vessels are pruned remains unclear. Here we show that pruning of the zebrafish caudal vein (CV) from ventral capillaries of the CV plexus in different transgenic embryos is driven by endothelial cell (EC) rearrangement, which involves EC nucleus migration, junction remodeling, and actin cytoskeleton remodeling. Further observation reveals a growing difference in blood flow velocity between the two vessels in CV pruning in zebrafish embryos. With this model, we identify the critical role of Kruppel-like factor 6a (klf6a) in CV pruning. Disruption of klf6a functioning impairs CV pruning in zebrafish. klf6a is required for EC nucleus migration, junction remodeling, and actin cytoskeleton dynamics in zebrafish embryos. Moreover, actin-related protein transgelin 2 (tagln2) is a direct downstream target of klf6a in CV pruning in zebrafish embryos. Together these results demonstrate that the klf6a-tagln2 axis regulates CV pruning by promoting EC rearrangement.

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