Pulmonary, Allergy, & Critical Care Division, Department of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Department of Systems Pharmacology and Translational Therapeutics and Center for Translational Targeted Therapeutics and Nanomedicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Nat Commun. 2018 Jul 11;9(1):2684. doi: 10.1038/s41467-018-05079-7.
Drug delivery by nanocarriers (NCs) has long been stymied by dominant liver uptake and limited target organ deposition, even when NCs are targeted using affinity moieties. Here we report a universal solution: red blood cell (RBC)-hitchhiking (RH), in which NCs adsorbed onto the RBCs transfer from RBCs to the first organ downstream of the intravascular injection. RH improves delivery for a wide range of NCs and even viral vectors. For example, RH injected intravenously increases liposome uptake in the first downstream organ, lungs, by ~40-fold compared with free NCs. Intra-carotid artery injection of RH NCs delivers >10% of the injected NC dose to the brain, ~10× higher than that achieved with affinity moieties. Further, RH works in mice, pigs, and ex vivo human lungs without causing RBC or end-organ toxicities. Thus, RH is a clinically translatable platform technology poised to augment drug delivery in acute lung disease, stroke, and several other diseases.
纳米载体（NCs）的药物递送长期以来一直受到肝脏摄取和有限的靶器官沉积的阻碍，即使使用亲和部分对 NCs 进行靶向。在这里，我们报告了一个通用的解决方案：红细胞（RBC）搭便车（RH），其中吸附在 RBC 上的 NC 从 RBC 转移到血管内注射后的第一个下游器官。RH 提高了广泛的 NC 甚至病毒载体的递送效率。例如，与游离 NC 相比，静脉内注射 RH 脂质体可使肺部等第一个下游器官的脂质体摄取增加约 40 倍。颈动脉内注射 RH-NC 可将超过 10%的注射 NC 剂量递送到大脑，比使用亲和部分实现的水平高约 10 倍。此外，RH 在小鼠、猪和离体人肺中均有效，而不会引起 RBC 或终末器官毒性。因此，RH 是一种具有临床转化潜力的平台技术，有望增强急性肺疾病、中风和其他几种疾病的药物递送。
