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

Abstract

Background Ischemic 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. Results 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. 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. Conclusion The results demonstrated that the developed McM/RNPs may serve as an effective and safe nanovehicles for I/R injury therapy. Graphic abstract

Nanoparticles in the diagnosis and treatment of vascular aging and related diseases

“…Besides, McM/RNPs can actively target and bind to inflammatory ECs, thus can serve as a shield between monocytes and ECs. 426 It has been revealed that resolvin D2 exhibited a critical role in the modulation of inflammation and tissue repair. Membrane-derived nanovesicles-encapsulated resolvin D2 pronouncedly enhanced its therapeutic efficacy in treating murine ischemic stroke.…”

Perspective insights into hydrogels and nanomaterials for ischemic stroke

“…Immunosuppressants are also the preferred candidates to modulate inflammation after IS ( Qiu et al, 2021 ); for example, mTOR inhibitor rapamycin (RNP) is a potent immunosuppressive agent with anti-inflammatory and anti-proliferative effects ( Querfurth and Lee, 2021 ). Monocytes membrane-coated RNP exerts chemo immunotherapeutic effects with high biosafety by retarding monocyte adhesion to endothelial cells and the recruitment of monocytes ( Wang et al, 2021d ). In another pathway, decreasing neutrophil infiltration by interfering with the interplay between neutrophil and endothelial cells blocks the inflammatory cascade triggered by the recruitment of peripheral inflammatory cells ( Planas, 2018 ; Jian et al, 2019 ).…”

Nanodecoys: A Quintessential Candidate to Augment Theranostic Applications for a Plethora of Diseases

“…The results obtained from the in vivo and in vitro experiments showed that the formulation prepared achieved binding to the inflammatory epithelial cells to inhibit the proliferation of inflammation in the injury site. Thus, the particle contributed immunotherapy against the ischemic stroke-induced rat model, and also enhanced the regeneration [ 15 ]. Macrophages are specialized innate immune cells responsible for maintaining the physiological ambiance.…”