Cardiovascular Research Institute, National University Health System, Singapore; School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
Nanomedicine. 2019 Jun;18:169-178. doi: 10.1016/j.nano.2019.02.024. Epub 2019 Mar 8.
Mammalian cell membranes are often incompatible with chemical modifications typically used to increase circulation half-life. Using cellular nanoghosts as a model, we show that proline-alanine-serine (PAS) peptide sequences expressed on the membrane surface can extend the circulation time of a cell membrane derived nanotherapeutic. Membrane expression of a PAS 40 repeat sequence decreased protein binding and resulted in a 90% decrease in macrophage uptake when compared with non-PASylated controls (P ≤ 0.05). PASylation also extended circulation half-life (t = 37 h) compared with non-PASylated controls (t = 10.5 h) (P ≤ 0.005), resulting in ~7-fold higher in vivo serum concentrations at 24 h and 48 h (P ≤ 0.005). Genetically engineered membrane expression of PAS repeats may offer an alternative to PEGylation and provide extended circulation times for cellular membrane-derived nanotherapeutics.
哺乳动物细胞膜通常与用于延长循环半衰期的化学修饰不兼容。我们以细胞纳米幽灵（cellular nanoghosts）作为模型，表明在细胞膜表面表达脯氨酸-丙氨酸-丝氨酸（PAS）肽序列可以延长细胞膜衍生的纳米治疗剂的循环时间。与非 PAS 化对照相比，膜表达的 PAS 40 重复序列减少了蛋白质结合，导致巨噬细胞摄取减少了 90%（P≤0.05）。与非 PAS 化对照相比，PAS 化还延长了循环半衰期（t=37 小时）（P≤0.005），导致 24 小时和 48 小时时体内血清浓度增加了约 7 倍（P≤0.005）。基因工程表达的 PAS 重复序列可能提供了一种替代聚乙二醇化的方法，并为细胞细胞膜衍生的纳米治疗剂提供了延长的循环时间。
