期刊
ADVANCED SCIENCE
卷 8, 期 20, 页码 -出版社
WILEY
DOI: 10.1002/advs.202101526
关键词
biomimetic nanoparticles; inflammatory microenvironment; microglia polarization; neuroprotection; O-2 generation; reperfusion injury; reactive oxygen species (ROS) consumption
资金
- National Natural Science Foundation of China [81872808]
- Program of Shanghai Academic Research Leader (China) [18XD1400500]
- Shanghai Municipal Science and Technology Major Project (China) [2018SHZDZX01]
- ZJLab
This biomimetic nanomedicine utilizes macrophage-disguised manganese dioxide nanospheres loaded with fingolimod to target the damaged brain in ischemic stroke, reducing oxidative stress, promoting microglial transition, and ultimately enhancing neuronal survival. This new strategy offers a multitargeted combined treatment approach for ischemic stroke.
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 (MnO2) 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. MnO2 nanosphere can consume excess hydrogen peroxide (H2O2) 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.
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