Department of Pharmaceutics, School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, China.
Institutes of Integrative Medicine of Fudan University, Shanghai 200040, China.
Sci Adv. 2019 Jul 10;5(7):eaau8301. doi: 10.1126/sciadv.aau8301. eCollection 2019 Jul.
Cerebral ischemia (CI) results from inadequate blood flow to the brain. The difficulty of delivering therapeutic molecules to lesions resulting from CI hinders the effective treatment of this disease. The inflammatory response following CI offers a unique opportunity for drug delivery to the ischemic brain and targeted cells because of the recruitment of leukocytes to the stroke core and penumbra. In the present study, neutrophils and monocytes were explored as cell carriers after selectively carrying cRGD liposomes, which effectively transmigrated the blood-brain barrier, infiltrated the cerebral parenchyma, and delivered therapeutic molecules to the injured sites and target cells. Our results showed the successful comigration of liposomes with neutrophils/monocytes and that both monocytes and neutrophils were important for successful delivery. Enhanced protection against ischemic injury was achieved in the CI/reperfusion model. The strategy presented here shows potential in the treatment of CI and other diseases related to inflammation.
脑缺血（CI）是由于大脑血液供应不足引起的。由于难以将治疗分子递送到 CI 引起的病变部位，因此阻碍了对这种疾病的有效治疗。CI 后的炎症反应为将药物递送到缺血性大脑和靶向细胞提供了独特的机会，因为白细胞被募集到中风核心和半影区。在本研究中，选择携带 cRGD 脂质体后，将中性粒细胞和单核细胞探索为细胞载体，脂质体有效地穿过血脑屏障，渗透到脑实质，并将治疗分子递送到损伤部位和靶细胞。我们的结果表明，脂质体与中性粒细胞/单核细胞的共迁移是成功的，单核细胞和中性粒细胞对成功递药都很重要。在 CI/再灌注模型中实现了对缺血性损伤的增强保护。这里提出的策略在治疗 CI 和其他与炎症相关的疾病方面显示出了潜力。
