Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Cancer Center at Illinois (CCIL), Urbana, IL 61801, USA.
Biomater Sci. 2024 Aug 6;12(16):4170-4180. doi: 10.1039/d4bm00625a.
Lipids have demonstrated tremendous promise for mRNA delivery, as evidenced by the success of Covid-19 mRNA vaccines. However, existing lipids are mostly used as delivery vehicles and lack the ability to monitor and further modulate the target cells. Here, for the first time, we report a class of unnatural lipids (azido-DOTAP) that can efficiently deliver mRNAs into cells and meanwhile metabolically label cells with unique chemical tags (, azido groups). The azido tags expressed on the cell membrane enable the monitoring of transfected cells, and can mediate subsequent conjugation of cargos efficient click chemistry for further modulation of transfected cells. We further demonstrate that the dual-functional unnatural lipid is applicable to different types of cells including dendritic cells, the prominent type of antigen presenting cells, potentially opening a new avenue to developing enhanced mRNA vaccines.
脂质在 mRNA 递送上显示出巨大的潜力，这一点从新冠 mRNA 疫苗的成功中可见一斑。然而，现有的脂质大多被用作递送载体，缺乏监测和进一步调节靶细胞的能力。在这里，我们首次报道了一类新型脂质（叠氮基-DOTAP），它可以有效地将 mRNA 递送入细胞，并同时用独特的化学标记物（叠氮基团）对细胞进行代谢标记。细胞膜上表达的叠氮标记物可以监测转染的细胞，并可以通过有效的点击化学将后续的 cargos 偶联上去，进一步调节转染的细胞。我们进一步证明，这种双功能的非天然脂质适用于不同类型的细胞，包括树突状细胞，这是一种突出的抗原呈递细胞类型，这可能为开发增强型 mRNA 疫苗开辟了新途径。
