Abstract：
Nucleic acid-based therapies are transforming medicine, but rely on an efficient delivery vehicle such as lipid nanoparticles (LNPs). Concerns exists in the nanomedicine field, that a large fraction of the LNPs in the ensemble does not contain any nucleic acid cargo and thus exert no functional effect. Nevertheless, how LNP lipid formulation, the LNP preparation method employed and nucleic acid cargo size correlates with the proportion of empty LNPs remains largely unexplored. Here we employ a well-established single particle based method to study nucleic acid loading heterogeneity in LNPs. We find that only a minor fraction of LNPs are \"empty\", both for LNPs loaded with siRNA, mRNA and plasmids. For clinically relevant LNPs for mRNA delivery, we never detected more than 16% empty nanoparticles in the ensemble. Thus employing standard LNP lipid-cargo combinations and preparation schemes results in LNPs with the potential to serve their biomedical function.
摘要：
基于核酸的疗法正在改变医学，但依赖于有效的递送载体,例如脂质纳米颗粒(LNP)。关注存在于纳米医学领域，集合中的大部分LNP不包含任何核酸货物,因此不发挥功能作用。然而，如何LNP脂质配方，所采用的LNP制备方法和核酸货物大小与空LNP的比例相关仍未被探索。在这里,我们采用建立良好的基于单颗粒的方法来研究LNP中的核酸负载异质性。我们发现只有一小部分LNP是“空的”，对于装载siRNA的LNP，mRNA和质粒。对于mRNA递送的临床相关LNP，我们从未在集合中检测到超过16%的空纳米粒子。因此,采用标准LNP脂质-货物组合和制备方案导致LNP具有发挥其生物医学功能的潜力。
