Macrophage‐Disguised Manganese Dioxide Nanoparticles for Neuroprotection by Reducing Oxidative Stress and Modulating Inflammatory Microenvironment in Acute Ischemic Stroke

Abstract

Reperfusion injury is still a major challenge that impedes neuronal survival in ischemic stroke. However, the current clinical treatments are remained on single pathological process, which are due to lack of comprehensive neuroprotective effects. Herein, a macrophage‐disguised honeycomb manganese dioxide (MnO 2 ) nanosphere loaded with fingolimod (FTY) is developed to salvage the ischemic penumbra. In particular, the biomimetic nanoparticles can accumulate actively in the damaged brain via macrophage‐membrane protein‐mediated recognition with cell adhesion molecules that are overexpressed on the damaged vascular endothelium. MnO 2 nanosphere can consume excess hydrogen peroxide (H 2 O 2 ) and convert it into desiderated oxygen (O 2 ), and can be decomposed in acidic lysosome for cargo release, so as to reduce oxidative stress and promote the transition of M1 microglia to M2 type, eventually reversing the proinflammatory microenvironment and reinforcing the survival of damaged neuron. This biomimetic nanomedicine raises new strategy for multitargeted combined treatment of ischemic stroke.

Macrophage-targeting gene silencing orchestrates myocardial microenvironment remodeling toward the anti-inflammatory treatment of ischemia-reperfusion (IR) injury

“…The in vivo macrophage targeting of Cy5-siRNA-containing NCs was further explored via flow cytometry. In the early stage of reperfusion (several hours to several days after IR), pro-inflammatory M1-type macrophages occupy a greatly larger proportion than anti-inflammatory M2-type macrophages in the injured myocardium [ [58] , [59] , [60] , [61] ]. Thus, the proportion of M1-or M2-type macrophages in the injured heart and the internalization of Cy5-siRNA-containing NCs in them were monitored.…”

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

“…Fingolimod-macrophage-disguised honeycomb MnO 2 nanoparticles reversed the brain pro-inflammatory microenvironment through consuming excessive H 2 O 2 and promoting M1 microglia switch to M2 phenotype. 424 Results from an ischemic stroke rat model and in vitro studies revealed that bioinspired melanin nanoparticles had excellent antioxidant effects. Apart from reducing oxidative stress, melanin nanoparticles reportedly play a role in alleviating the production of inflammatory factors.…”

Cell Membrane-Derived Vesicle: A Novel Vehicle for Cancer Immunotherapy

“…The typical process of isolating cellular vesicles consists of several steps ( Figure 1A ). Firstly, the parental cells are harvested and resuspended in a hypotonic buffer, rendering the cytoplasm swollen and susceptible to fragmentation by external forces ( 6 , 7 ). Then, if the cytoplasmic components are to be removed, cells usually need to undergo approximately five freeze-thawing cycles and dounce homogenization to release intracellular proteins ( 6 , 7 ).…”

“…Firstly, the parental cells are harvested and resuspended in a hypotonic buffer, rendering the cytoplasm swollen and susceptible to fragmentation by external forces ( 6 , 7 ). Then, if the cytoplasmic components are to be removed, cells usually need to undergo approximately five freeze-thawing cycles and dounce homogenization to release intracellular proteins ( 6 , 7 ). Next, cell membranes are separated from other cellular components by continuous high-speed or density gradient centrifugation.…”

“…Next, cell membranes are separated from other cellular components by continuous high-speed or density gradient centrifugation. For example, the cells were subjected to centrifugation at 1000 g, 10000 g, and 100000 g to remove the nuclei, organelles, and other impurities, respectively ( 6 ). For density gradient centrifugation, cell membranes were prepared by centrifugation through discontinuous 30-40-55% sucrose (w/v) density gradient.…”