Functionalized nanoparticles with monocyte membranes and rapamycin achieve synergistic chemoimmunotherapy for reperfusion-induced injury in ischemic stroke

Yanyun Wang,Juanjuan Shan,Guixue Wang,Juhui Qiu,Yiliang Li,Yi Wang,Shuyu Li,Wei Gu,Xiping Liang,Yuliang Cui

doi:10.1186/s12951-021-01067-0

Abstract

BackgroundIschemic stroke is an acute and severe neurological disease, and reperfusion is an effective way to reverse brain damage after stroke. However, reperfusion causes secondary tissue damage induced by inflammatory responses, called ischemia/reperfusion (I/R) injury. Current therapeutic strategies that control inflammation to treat I/R are less than satisfactory.ResultsWe 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. 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. 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. 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. Importantly, in vivo animal studies revealed good safety for McM/RNPs treatment.ConclusionThe results demonstrated that the developed McM/RNPs may serve as an effective and safe nanovehicles for I/R injury therapy.Graphic abstract

Highlights

Ischemic stroke is an acute and severe neurological disease, and reperfusion is an effective way to reverse brain damage after stroke
The transmission electron microscopy (TEM) measurements revealed that, compared with uncoated Rapamycin‐loaded PLGA nanoparticles (RNPs), the diameter of monocyte membrane (McM)/ RNPs almost increased by 16 nm, which was attributed to the thickness of McM is about 8 nm
The TEM image results showed that McM had the structure of cell membrane (Additional file 1: Fig. S1) and McM/RNPs displayed a characteristic “core–shell” structure, which was consistent with unilamellar membrane coating around the polymeric core (Fig. 1d)

Summary

Introduction

Ischemic stroke is an acute and severe neurological disease, and reperfusion is an effective way to reverse brain damage after stroke. Reperfusion causes secondary tissue damage induced by inflammatory responses, called ischemia/reperfusion (I/R) injury. Reperfusion for cerebral ischemia is an effective approach to reducing disability when administered within 4.5 h after stroke [3]. Cerebral ischemia/reperfusion (I/R) can lead to serious injury to the brain, neural cells, and even the entire body because of the abrupt recovery of blood flow and. 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 [7]. Overall, reducing local microglial activation and inflammation through endothelial cells is a potential way to control the inflammation after cerebral I/R

Methods

Results

Conclusion