Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA 02155, USA.
Sci Adv. 2020 Jul 24;6(30):eabb4429. doi: 10.1126/sciadv.abb4429. eCollection 2020 Jul.
Safe and efficient delivery of blood-brain barrier (BBB)-impermeable cargos into the brain through intravenous injection remains a challenge. Here, we developed a previously unknown class of neurotransmitter-derived lipidoids (NT-lipidoids) as simple and effective carriers for enhanced brain delivery of several BBB-impermeable cargos. Doping the NT-lipidoids into BBB-impermeable lipid nanoparticles (LNPs) gave the LNPs the ability to cross the BBB. Using this brain delivery platform, we successfully delivered amphotericin B (AmB), antisense oligonucleotides (ASOs) against tau, and genome-editing fusion protein (-27)GFP-Cre recombinase into the mouse brain via systemic intravenous administration. We demonstrated that the NT-lipidoid formulation not only facilitates cargo crossing of the BBB, but also delivery of the cargo into neuronal cells for functional gene silencing or gene recombination. This class of brain delivery lipid formulations holds great potential in the treatment of central nervous system diseases or as a tool to study the brain function.
通过静脉注射将血脑屏障（BBB）不可渗透的有效载荷安全有效地递送到大脑仍然是一个挑战。在这里，我们开发了一类以前未知的神经递质衍生脂质体（NT-脂质体），作为增强几种 BBB 不可渗透的有效载荷脑内传递的简单有效的载体。将 NT-脂质体掺杂到 BBB 不可渗透的脂质纳米颗粒（LNPs）中，使 LNPs 具有穿过 BBB 的能力。使用这种脑内传递平台，我们通过系统静脉内给药成功地将两性霉素 B（AmB）、针对 tau 的反义寡核苷酸（ASO）和基因组编辑融合蛋白（-27）GFP-Cre 重组酶递送到小鼠大脑中。我们证明，NT-脂质体配方不仅促进了货物穿过 BBB，还将货物递送到神经元细胞中，以实现功能性基因沉默或基因重组。这类脑内传递脂质制剂在治疗中枢神经系统疾病或作为研究大脑功能的工具方面具有巨大的潜力。
