Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, 230027, P. R. China.
Department of Pediatrics, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, P. R. China.
Adv Mater. 2021 Jan;33(3):e2006160. doi: 10.1002/adma.202006160. Epub 2020 Dec 9.
Nanomedicines that target specific blood cells represent an emerging strategy to improve drug biodistribution. However, the protein corona usually disrupts nanomedicine targeting to cells and tissues. Herein, instead of exploring synthetic methods to mitigate the impact of the protein corona, its natural interactions with blood cells are leveraged and turn the protein corona into an active ingredient in treating lung inflammation. It is discovered that molecularly engineered liposomes with inverse phosphocholine lipids rapidly enrich complement fragment iC3b by "voluntary opsonization," which triggers neutrophil hijacking through complement receptor 3 phagocytosis. This neutrophil targeting is cell-state dependent as only those activated by acute inflammation display efficient neutrophil reconstruction. The liposome-loaded neutrophils migrate across the alveolar-capillary barrier, accumulate in the inflamed lung parenchyma within hours, and release their payloads to kill the bacteria. This work shows that, in addition to biological cells, the protein corona can be a new platform for active and precision nanomedicine.
针对特定血细胞的纳米药物代表了一种改善药物生物分布的新兴策略。然而，蛋白质冠通常会破坏纳米药物对细胞和组织的靶向作用。在此，我们没有探索减轻蛋白质冠影响的合成方法，而是利用其与血细胞的天然相互作用，将蛋白质冠转化为治疗肺部炎症的有效成分。研究发现，具有反向磷酸胆碱脂质的分子工程化脂质体通过“自愿调理”快速富集补体片段 iC3b，通过补体受体 3 吞噬作用触发中性粒细胞劫持。这种中性粒细胞靶向作用依赖于细胞状态，只有那些被急性炎症激活的细胞才会表现出有效的中性粒细胞重建。负载脂质体的中性粒细胞穿过肺泡毛细血管屏障，在数小时内积聚在发炎的肺实质中，并释放其有效载荷来杀死细菌。这项工作表明，除了生物细胞，蛋白质冠可以成为主动和精准纳米医学的新平台。
