Journal
NANO LETTERS
Volume 19, Issue 7, Pages 4470-4477Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.9b01282
Keywords
Inflammatory neutrophil recognition; platelet-mimetic nanoparticles; piceatannol; superparamagnetic iron oxide; acute ischemic stroke
Categories
Funding
- National Natural Science Foundation of China [81773664, 81473153, 81503003]
- National Basic Research Program of China [2015CB755504]
- 111 Project from the Ministry of Education of China
- State Administration of Foreign Expert Affairs of China [111-2-07, B17047]
- Fundamental Research Funds for the Central Universities of China [2632017ZD06]
- Open Project of State Key Laboratory of Natural Medicines [SKLNMZZCX201811]
- Double First-Class University project [CPU2018GY47, CPU2018GF10]
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Neutrophils are implicated in numerous inflammatory diseases, and especially in acute ischemic stroke (AIS). The unchecked migration of neutrophils into cerebral ischemic regions, and their subsequent release of reactive oxygen species, are considered the primary causes of reperfusion injury following AIS. Reducing the infiltration of inflammatory neutrophils may therefore be a useful therapy for AIS. Here, inspired by the specific cell-cell recognition that occurs between platelets and inflammatory neutrophils, we describe platelet-mimetic nanoparticles (PTNPs) that can be used to directly recognize, intervene, and monitor inflammatory neutrophils in the AIS treatment and therapeutic evaluation. We demonstrate that PTNPs, coloaded with piceatannol, a selective spleen tyrosine kinase inhibitor, and superparamagnetic iron oxide (SPIO), a T2 contrast agent, can successfully recognize adherent neutrophils via platelet membrane coating. The loaded piceatannol could then be delivered to adherent neutrophils and detach them into circulation, thus decreasing neutrophil infiltration and reducing infarct size. Moreover, when coupled with magnetic resonance imaging, internalized SPIO could be used to monitor the inflammatory neutrophils, associated with therapeutic effects, in real time. This approach is an innovative method for both the treatment and therapeutic evaluation of AIS, and provides new insights into how to treat and monitor neutrophil-associated diseases.
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