Department of Materials, Department of Bioengineering, and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
Department of Infectious Diseases, Imperial College London, London, W2 1PG, UK.
Adv Mater. 2020 Dec;32(48):e2003598. doi: 10.1002/adma.202003598. Epub 2020 Oct 26.
Uncontrolled inflammation is a major pathological factor underlying a range of diseases including autoimmune conditions, cardiovascular disease, and cancer. Improving localized delivery of immunosuppressive drugs to inflamed tissue in a non-invasive manner offers significant promise to reduce severe side effects caused by systemic administration. Here, a neutrophil-mediated delivery system able to transport drug-loaded nanocarriers to inflamed tissue by exploiting the inherent ability of neutrophils to migrate to inflammatory tissue is reported. This hybrid system (neutrophils loaded with liposomes ex vivo) efficiently migrates in vitro following an inflammatory chemokine gradient. Furthermore, the triggered release of loaded liposomes and reuptake by target macrophages is studied. The migratory behavior of liposome-loaded neutrophils is confirmed in vivo by demonstrating the delivery of drug-loaded liposomes to an inflamed skeletal muscle in mice. A single low-dose injection of the hybrid system locally reduces inflammatory cytokine levels. Biodistribution of liposome-loaded neutrophils in a human-disease-relevant myocardial ischemia reperfusion injury mouse model after i.v. injection confirms the ability of injected neutrophils to carry loaded liposomes to inflammation sites. This strategy shows the potential of nanocarrier-loaded neutrophils as a universal platform to deliver anti-inflammatory drugs to promote tissue regeneration in inflammatory diseases.
不受控制的炎症是一系列疾病的主要病理因素，包括自身免疫性疾病、心血管疾病和癌症。以非侵入性的方式将免疫抑制药物更有效地递送到炎症组织中，可以显著降低全身给药引起的严重副作用。在这里，我们报道了一种中性粒细胞介导的递药系统，该系统能够利用中性粒细胞向炎症组织迁移的固有能力，将载药纳米载体递送到炎症组织中。这种混合系统（体外负载脂 质体的中性粒细胞）能够在炎症趋化因子梯度的作用下在体外有效迁移。此外，还研究了负载脂质体的触发释放和靶巨噬细胞的再摄取。通过证明载药脂质体递送到小鼠炎症性骨骼肌中，在体内证实了负载脂质体的中性粒细胞的迁移行为。单次低剂量注射该混合系统可局部降低炎症细胞因子水平。静脉注射后，负载脂 质体的中性粒细胞在与人相关的心肌缺血再灌注损伤小鼠模型中的分布证实了注射的中性粒细胞能够将负载的脂质体带到炎症部位。该策略显示了负载纳米载体的中性粒细胞作为一种通用平台的潜力，可将抗炎药物递送到炎症组织中，以促进炎症性疾病中的组织再生。
