Department of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
Department of Neuroscience, Tufts University, Boston, MA, 02111, USA.
Angew Chem Int Ed Engl. 2020 Aug 24;59(35):14957-14964. doi: 10.1002/anie.202004994. Epub 2020 Jun 15.
Developing safe and efficient delivery systems for therapeutic biomacromolecules is a long-standing challenge. Herein, we report a newly developed combinatorial library of cholesteryl-based disulfide bond-containing biodegradable cationic lipidoid nanoparticles. We have identified a subset of this library which is effective for protein and mRNA delivery in vitro and in vivo. These lipidoids showed comparable transfection efficacies but much lower cytotoxicities compared to the Lpf2k in vitro. In vivo studies in adult mice demonstrated the successful delivery of genome engineering protein and mRNA molecules in the skeletal muscle (via intramuscular injection), lung and spleen (via intravenous injection), and brain (via lateral ventricle infusion).
开发安全有效的治疗性生物大分子递药系统是一个长期存在的挑战。在此，我们报告了一种新开发的基于胆固醇的含二硫键的可生物降解阳离子类脂纳米粒子组合文库。我们已经鉴定出该文库的一个亚组，它可有效地用于体外和体内蛋白质和 mRNA 的递药。与 Lpf2k 相比，这些类脂纳米载体表现出相当的转染效率，但细胞毒性要低得多。在成年小鼠的体内研究中，成功地将基因组工程蛋白和 mRNA 递送到了骨骼肌（通过肌肉内注射）、肺和脾（通过静脉注射）以及脑（通过侧脑室输注）。
