Ischemic stroke is the most common type of stroke, seriously endangering the lives and health of the population. The main treatment methods include thrombolysis and thrombectomy in the acute phase and drug therapy. Recent studies have found that inflammatory responses play a significant role in the development of ischemic stroke, and microglia are the main contributors to early neuroinflammation. However, problems such as the blood-brain barrier and poor targeting prevent anti-inflammatory drugs from being effective in treatment. This study presents a nanogel modified with multiple polypeptides, designed to effectively cross the blood-brain barrier, specifically target microglia in ischemic and hypoxic regions, and regulate the release of the anti-inflammatory drug thalidomide. This approach aims to inhibit neuroinflammation and treat ischemic stroke. In vitro results demonstrate that the nanogel can reduce the expression of the microglial inflammatory marker TNF-α, while in vivo results show that it improves learning, memory, and motor function, and mitigates anxiety and depressive behaviors associated with neuroinflammation in ischemic stroke. Overall, we have developed a drug-loaded nanogel targeting TNF-α in microglia within ischemic and hypoxic areas, enhancing anti-inflammatory effects and offering a novel therapeutic strategy for ischemic stroke. • Three biologically active polypeptides were linked to the poly(acrylic acid) backbone. • Nanogels could penetrate the blood-brain barrier and target ischemic regions. • Thalidomide had anti-inflammatory effects on microglia. • Nanogel treatment improved the neurological function of mice with ischemic stroke. .•The function of nanogels in vivo was achieved by targeting microglia.
Xia et al. (Sun,) studied this question.
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