To decrease inflammation, protein nanoparticle-conjugated doxorubicin (DOX) can alleviate neurological damage in stroke by inducing neutrophil apoptosis. Neutrophil-derived nanovesicles can alleviate inflammation to protect against ischemic stroke injury by decreasing adhesion neutrophils with endothelial cells. The BBB and inflammatory endothelial cells are critical for both drug delivery and inflammatory cell infiltrating in stroke therapies. There are two main approaches to abate inflammation: reducing the inflammatory cells penetrating into the injury site from the blood and inhibiting inflammatory cell activation and proliferation in the focal site. Reducing neuroinflammation has become an effective adjunct therapy to improve outcomes. Most of the mechanisms are nanoparticles with prolonged blood circulation time, reduced clearance rate, improved BBB penetration ability, and enhanced brain accumulation. With the rapid development of nanotechnology, nanoparticles with different components have recently developed and can efficiently reverse reperfusion-induced injury in ischemic stroke. Overall, reducing local microglial activation and inflammation through endothelial cells is a potential way to control the inflammation after cerebral I/R. The permeability of endothelial cells is also critical for the blood–brain barrier (BBB) and inflammation in the ischemia–reperfusion brain, with a vicious circle. Furthermore, focal brain inflammation aggravates secondary brain injury by exacerbating blood–brain barrier damage and microvascular failure. Therefore, deletion of chemokines, such as mineralocorticoid receptor and transforming growth factor beta-activated kinase 1, can alter inflammation and reduce infarct volume during cerebral ischemia. In addition, microglia in the focal injury site can activate infiltrating macrophages and other inflammatory cells. A growing body of evidence suggests that inflammatory responses persist throughout the entire brain for a long time and affect patients' long-term neurological outcomes. With intensive study of post ischemic microenvironment, apoptotic and dead neuronal cells release cellular factors, and cytokines induce strong inflammation in the injured brain region. Accordingly, there is an urgent need for innovative and effective therapeutic approaches for cerebral I/R. However, cerebral ischemia/reperfusion (I/R) can also lead to serious injury to the brain, neural cells, and even the entire body because of the abrupt recovery of blood flow and strong inflammation. Reperfusion for cerebral ischemia is an effective approach to reducing disability when administered within 4.5 h after stroke. Ischemic stroke represents ~ 71% of all strokes worldwide and is associated with infarction of the brain, spinal cord, or retina. Graphic abstractĭespite recent therapeutic advances, stroke remains the leading cause of disability with high social and economic burden. The results demonstrated that the developed McM/RNPs may serve as an effective and safe nanovehicles for I/R injury therapy. Importantly, in vivo animal studies revealed good safety for McM/RNPs treatment. In a rat I/R injury model, McM/RNPs exhibited improved active homing to I/R injury areas and greatly ameliorated neuroscores and infarct volume. Subsequently, McM/RNPs can penetrate the endothelium to reach the injury site, similar to a sword, and release the RAP drug to inhibit the proliferation of inflammatory cells. The fabricated McM/RNPs can actively target and bind to inflammatory endothelial cells, which inhibit the adhesion of monocytes to the endothelium, thus acting as a shield. We report a kind of shield and sword nano-soldier functionalized nanoparticles (monocyte membranes-coated rapamycin nanoparticles, McM/RNPs) that can reduce inflammation and relieve I/R injury by blocking monocyte infiltration and inhibiting microglia proliferation. Current therapeutic strategies that control inflammation to treat I/R are less than satisfactory. However, reperfusion causes secondary tissue damage induced by inflammatory responses, called ischemia/reperfusion (I/R) injury. Ischemic stroke is an acute and severe neurological disease, and reperfusion is an effective way to reverse brain damage after stroke.

Functionalized core shell nanoparticles